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<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F22289912%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F22289912%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="FzxzckO79zoFCvjW80OJFIMPG7lZ2eZhWmhEPahtJab9wWpMLjrL9Qiteb3bVPxB">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="FzxzckO79zoFCvjW80OJFIMPG7lZ2eZhWmhEPahtJab9wWpMLjrL9Qiteb3bVPxB">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="FzxzckO79zoFCvjW80OJFIMPG7lZ2eZhWmhEPahtJab9wWpMLjrL9Qiteb3bVPxB">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 22289912 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 22289912"/>
|
||
<input type="hidden" name="email-subject-hash" value="6cc47a01f29b52cb0cacc2390bd1773c9c46bfb5f009745a4e734fd4b5769f90"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="FzxzckO79zoFCvjW80OJFIMPG7lZ2eZhWmhEPahtJab9wWpMLjrL9Qiteb3bVPxB">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="FzxzckO79zoFCvjW80OJFIMPG7lZ2eZhWmhEPahtJab9wWpMLjrL9Qiteb3bVPxB">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="FzxzckO79zoFCvjW80OJFIMPG7lZ2eZhWmhEPahtJab9wWpMLjrL9Qiteb3bVPxB">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="FzxzckO79zoFCvjW80OJFIMPG7lZ2eZhWmhEPahtJab9wWpMLjrL9Qiteb3bVPxB">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="FzxzckO79zoFCvjW80OJFIMPG7lZ2eZhWmhEPahtJab9wWpMLjrL9Qiteb3bVPxB">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="22289912">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://doi.org/10.1113/jphysiol.2012.228205"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3058&itool=Abstract-def&log$=linkouticon&uid=22289912&db=pubmed&nlmid=0266262"
|
||
title="See full text options at Wiley"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Wiley"
|
||
data-ga-label="22289912"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7325-10-JP_logo_FREE.JPG" alt="Wiley full text link"><span class="text">
|
||
|
||
Wiley
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/22289912/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=22289912&db=pubmed&nlmid=0266262"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="22289912"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/22289912/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/22289912/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="22289912" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F22289912%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="FzxzckO79zoFCvjW80OJFIMPG7lZ2eZhWmhEPahtJab9wWpMLjrL9Qiteb3bVPxB"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region"><button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title">
|
||
Display options
|
||
</div><div class="content"><div class="format-container"><span class="option-label">
|
||
Format
|
||
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Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13
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Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13
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Mutations in Kv3.3 cause spinocerebellar ataxia type 13 (SCA13). Depending on the causative mutation, SCA13 is either a neurodevelopmental disorder that is evident in infancy or a progressive neurodegenerative disease that emerges during adulthood. Previous studies did not clarify the relationship between these distinct clinical phenotypes and the effects of SCA13 mutations on Kv3.3 function. The F448L mutation alters channel gating and causes early-onset SCA13. R420H and R423H suppress Kv3 current amplitude by a dominant negative mechanism. However, R420H results in the adult form of the disease whereas R423H produces the early-onset, neurodevelopmental form with significant clinical overlap with F448L. Since individuals with SCA13 have one wild type and one mutant allele of the Kv3.3 gene, we analysed the properties of tetrameric channels formed by mixtures of wild type and mutant subunits. We report that one R420H subunit and at least one R423H subunit can co-assemble with the wild type protein to form active channels. The functional properties of channels containing R420H and wild type subunits strongly resemble those of wild type alone. In contrast, channels containing R423H and wild type subunits show significantly altered gating, including a hyperpolarized shift in the voltage dependence of activation, slower activation, and modestly slower deactivation. Notably, these effects resemble the modified gating seen in channels containing a mixture of F448L and wild type subunits, although the F448L subunit slows deactivation more dramatically than the R423H subunit. Our results suggest that the clinical severity of R423H reflects its dual dominant negative and dominant gain of function effects. However, as shown by R420H, reducing current amplitude without altering gating does not result in infant onset disease. Therefore, our data strongly suggest that changes in Kv3.3 gating contribute significantly to an early age of onset in SCA13.
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<p> Figure 1. One R420H subunit can incorporate into functional Kv3.3 channels </p>
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<div class="figure-caption-contents"><i> A </i> , RNA encoding…</div>
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Figure 1. One R420H subunit can incorporate into functional Kv3.3 channels
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<div class="figure-caption-contents"><i>A</i>, RNA encoding wild type and R420H subunits was injected into oocytes at the indicated ratios (WT:R420H). Currents were evoked by pulsing from −90 mV to +40 mV. Representative examples are shown. <i>B</i>, bar graph shows normalized peak current amplitudes measured at +40 mV for the indicated ratios of wild type and R420H RNA (2nd bar from left at each ratio). Values are provided as mean ± SEM, <i>n</i> = 19–45. Significance was tested using a one-way ANOVA followed by 2 sample <i>t</i> test, <i>P</i> < 0.05: *different from 1:0; **different from 1:0.5; ***different from 1:1; ****different from 1:2; *****different from 1:4. Also shown are the predictions of the binomial distribution for the hypotheses that one mutant subunit abolishes activity (1st bar) or that one (3rd bar) or two (4th bar) mutant subunits can incorporate into functional channels. The graph differs somewhat from published data because the amount of wild type RNA used in previous experiments was sometimes beyond the linear response range (Waters <i>et al.</i> 2006). <i>C</i>, Kv3.3-IR and R420H subunits were expressed at the indicated ratios (IR:R420H) or Kv3.3-IR and wild type were expressed alone. Current traces were evoked by pulsing from −80 mV to +40 mV. Representative examples, scaled to the same amplitude and overlaid, are shown. <i>D</i>, box plot shows normalized <i>I</i><sub>500ms</sub>/<i>I</i><sub>peak</sub> values measured at +40 mV for the indicated ratios of Kv3.3-IR and R420H subunits. For comparison, values obtained with Kv3.3-IR or wild type expressed alone are also shown. Indicated pairs differed significantly by one-way ANOVA followed by 2 sample <i>t</i> test: §<i>P</i> < 0.00001; *<i>P</i> < 0.05 (Kv3.3-IR, <i>n</i> = 21; 1:1, <i>n</i> = 18; 1:4, <i>n</i> = 13; wild type, <i>n</i> = 15).</div>
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<p> Figure 2. R420H subunits have little effect… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 2. R420H subunits have little effect on the functional properties of Kv3.3 channels </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i> A… </i></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 2. R420H subunits have little effect on the functional properties of Kv3.3 channels
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i>A</i>, normalized conductance has been plotted as a function of voltage for wild type Kv3.3 expressed alone (▪, <i>n</i> = 155) or with R420H at a 1:1 ratio (□, <i>n</i> = 29). Values are provided as mean ± SEM. Here and in subsequent figures, if error bars are not visible they are smaller than the size of the symbol. Data sets were fitted with single Boltzmann functions (continuous lines). Midpoint voltages and slope factors are shown in Table 1. Results obtained at ratios of 1:2 and 1:4 did not differ significantly from 1:1 (data not shown). <i>B</i>, currents were evoked by pulsing from –90 mV to voltages ranging from +10 to +70 mV in 10 mV increments. Current traces were fitted with a single exponential function to estimate the time constant for activation (τ<sub>act</sub>), which has been plotted <i>versus</i> voltage. Data are shown for wild type expressed alone (▪, <i>n</i> = 48) or co-injected with R420H at ratios of 1:1 (□, <i>n</i> = 9) and 1:2 (o, <i>n</i> = 9). Values are provided as mean ± SEM. Values of τ<sub>act</sub> did not differ significantly (one-way ANOVA followed by 2 sample <i>t</i> test, <i>P</i>≥ 0.05). <i>C</i>, tail currents were recorded in a high Rb<sup>+</sup> bath solution by repolarizing from +40 mV to voltages ranging from <b>−</b>25 to –90 mV in 5 mV increments. Traces were fitted with a single exponential function to estimate the time constant for deactivation (τ<sub>deact</sub>), which has been plotted <i>versus</i> repolarization voltage. Data are shown for wild type expressed alone (▪, <i>n</i> = 36) or with R420H at a 1:1 ratio (□, <i>n</i> = 11). Values are provided as mean ± SEM. Between –25 and –40 mV, values of τ<sub>deact</sub> differed significantly by ANOVA followed by 2 sample <i>t</i> test (*<i>P</i> < 0.05). At ratios of 1:2 and 1:4, tail currents were too small to measure. <i>D</i>, tail currents were recorded in a high K<sup>+</sup> bath solution by repolarizing from +40 mV to voltages ranging from <b>−</b>15 to <b>−</b>90 mV in 5 mV increments. Traces were fitted with a single exponential function to estimate τ<sub>deact</sub>, which has been plotted <i>versus</i> repolarization voltage. Data are shown for wild type expressed alone (▪, <i>n</i> = 9) or with R420H at a 1:1 ratio (□, <i>n</i> = 11). Values are provided as mean ± SEM. Values of τ<sub>deact</sub> did not differ significantly by ANOVA followed by 2 sample <i>t</i> test (<i>P</i>≥ 0.05).</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="2"
|
||
data-label-slug="figure-3">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df4/3413486/7f1bc5543404/tjp0590-1599-f3.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-2"
|
||
role="button"
|
||
data-image-width="720"
|
||
data-image-height="916"
|
||
data-image-alt="Figure 3"
|
||
data-pmc-id="PMC3413486"
|
||
data-figure-id="fig03">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-2"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df4/3413486/94d96a245797/tjp0590-1599-f3.gif"
|
||
alt="Figure 3" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="720">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="916">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 3. R420H mutation does not generate… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 3. R420H mutation does not generate detectable gating pore currents in oocytes </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Data are… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 3. R420H mutation does not generate detectable gating pore currents in oocytes
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Data are shown for: <i>A</i>, WT:W495F expressed alone; <i>B</i>, WT:W495F and R420H:W495F expressed at a 1:1 ratio; <i>C</i>, uninjected oocytes; and <i>D</i>, oocytes injected with RNase-free water (mock-injected). Each panel shows representative, unsubtracted current traces recorded at pH 7.2 (left) or 5.5 (centre) by pulsing from –90 mV to voltages ranging from −90 to +60 mV in 10 mV increments. Dashed lines indicate the 0 current level. Right: current amplitudes measured at pH 7.2 (squares) or 5.5 (circles) have been plotted <i>versus</i> voltage. Values are provided as mean ± SEM. The continuous line shows a linear regression fit to the pH 7.2 data.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="3"
|
||
data-label-slug="figure-4">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df4/3413486/28c46746b04b/tjp0590-1599-f4.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-3"
|
||
role="button"
|
||
data-image-width="480"
|
||
data-image-height="454"
|
||
data-image-alt="Figure 4"
|
||
data-pmc-id="PMC3413486"
|
||
data-figure-id="fig04">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-3"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df4/3413486/e5b0cd04d5f3/tjp0590-1599-f4.gif"
|
||
alt="Figure 4" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="480">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="454">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 4. At least one R423H subunit… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 4. At least one R423H subunit can incorporate into functional Kv3.3 channels </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i> A </i> ,…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 4. At least one R423H subunit can incorporate into functional Kv3.3 channels
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i>A</i>, RNA encoding wild type and R423H subunits was injected into oocytes at the indicated ratios (WT:R423H). Currents were evoked by pulsing from −90 mV to +40 mV. Representative examples are shown. <i>B</i>, bar graph shows normalized peak current amplitudes measured at +40 mV for the indicated ratios of wild type and R423H (2nd bar from left at each ratio). Values are provided as mean ± SEM, <i>n</i> = 3–32. Indicated values differed significantly from wild type expressed alone by one-way ANOVA followed by 2 sample <i>t</i> test (*<i>P</i> < 0.05). Also shown are the predictions of the binomial distribution for the hypotheses that one mutant subunit abolishes activity (1st bar) or that one (3rd bar) or two (4th bar) mutant subunits can incorporate into functional channels. The graph differs somewhat from published data because the amount of wild type RNA used in previous experiments was sometimes beyond the linear response range (Figueroa <i>et al.</i> 2010). <i>C</i>, Kv3.3-IR and R423H subunits were expressed at the indicated ratios (IR:R423H) or Kv3.3-IR and wild type were expressed alone. Current traces were evoked by pulsing from −80 mV to +40 mV. Representative examples, scaled to the same amplitude and overlaid, are shown. <i>D</i>, box plot shows normalized <i>I</i><sub>500ms</sub>/<i>I</i><sub>peak</sub> values measured at +40 mV for the indicated ratios of Kv3.3-IR and R423H subunits. For comparison, values obtained with Kv3.3-IR or wild type expressed alone are also shown. Indicated pairs differed significantly by one-way ANOVA followed by 2 sample <i>t</i> test: §<i>P</i> < 0.00001; ns, not significant (Kv3.3-IR, <i>n</i> = 21; 1:1, <i>n</i> = 10; 1:4, <i>n</i> = 5; wild type, <i>n</i> = 15). <i>E</i>, RNA encoding R423H (2 ng or 16 ng, as indicated) was injected into oocytes. Traces were recorded by stepping from –90 mV to voltages ranging from <b>−</b>80 to +70 mV in 10 mV increments. Representative results are shown.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="4"
|
||
data-label-slug="figure-5">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df4/3413486/765e46cc5e5c/tjp0590-1599-f5.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-4"
|
||
role="button"
|
||
data-image-width="360"
|
||
data-image-height="1229"
|
||
data-image-alt="Figure 5"
|
||
data-pmc-id="PMC3413486"
|
||
data-figure-id="fig05">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-4"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df4/3413486/157f9011bcf1/tjp0590-1599-f5.gif"
|
||
alt="Figure 5" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="360">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1229">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 5. R423H subunits affect the specialized… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 5. R423H subunits affect the specialized gating properties of Kv3.3 channels </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i> A </i> , normalized…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 5. R423H subunits affect the specialized gating properties of Kv3.3 channels
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i>A</i>, normalized conductance has been plotted as a function of voltage for wild type Kv3.3 (▪, <i>n</i> = 155) or R423H (•, <i>n</i> = 4) expressed alone or for wild type and R423H expressed at a 1:1 ratio (□, <i>n</i> = 35). Values are provided as mean ± SEM. Data sets were fitted with single Boltzmann functions (continuous lines). Midpoint voltages and slope factors are shown in Table 1. <i>B</i>, current traces were fitted with a single exponential function to estimate τ<sub>act</sub>, which has been plotted <i>versus</i> voltage. Data are shown for wild type (▪, <i>n</i> = 48) or R423H (•, <i>n</i> = 4) expressed alone and for wild type and R423H expressed at a 1:1 ratio (□, <i>n</i> = 7). Values are provided as mean ± SEM. As indicated, R423H expressed alone or in a 1:1 ratio with wild type differed significantly from wild type expressed alone by one-way ANOVA followed by 2 sample <i>t</i> test (*<i>P</i> < 0.05). <i>C</i>, tail currents were recorded in a high Rb<sup>+</sup> bath solution by repolarizing from +40 mV to voltages ranging from <b>−</b>25 to –90 mV. Traces were fitted with a single exponential function to estimate τ<sub>deact</sub>, which has been plotted <i>versus</i> repolarization voltage. Data are shown for wild type expressed alone (▪, <i>n</i> = 36) or with R423H at a 1:1 ratio (□, <i>n</i> = 4). Values are provided as mean ± SEM. Values of τ<sub>deact</sub> differed significantly by ANOVA followed by 2 sample <i>t</i> test (*<i>P</i> < 0.05). When R423H was expressed alone, tail currents were too small to measure. <i>D</i>, tail currents were recorded in a high K<sup>+</sup> bath solution by repolarizing from +40 mV to voltages ranging from <b>−</b>40 to –80 mV in 10 mV increments. Traces were fitted with a single exponential function to estimate τ<sub>deact</sub>, which has been plotted <i>versus</i> repolarization voltage. Data are shown for wild type expressed alone (▪, <i>n</i> = 8–11) or with R423H at a 1:1 ratio (□, <i>n</i> = 19). Values are provided as mean ± SEM. Values of τ<sub>deact</sub> differed significantly by ANOVA followed by 2 sample <i>t</i> test (#<i>P</i> < 0.0001; ‡<i>P</i> < 0.0005; **<i>P</i> < 0.001).</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="5"
|
||
data-label-slug="figure-6">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df4/3413486/d07191ffe9e6/tjp0590-1599-f6.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-5"
|
||
role="button"
|
||
data-image-width="720"
|
||
data-image-height="202"
|
||
data-image-alt="Figure 6"
|
||
data-pmc-id="PMC3413486"
|
||
data-figure-id="fig06">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-5"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df4/3413486/ff9c395c8e9b/tjp0590-1599-f6.gif"
|
||
alt="Figure 6" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="720">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="202">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 6. R423H mutation does not generate… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 6. R423H mutation does not generate detectable gating pore currents in oocytes </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> WT-W495F and… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 6. R423H mutation does not generate detectable gating pore currents in oocytes
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">WT-W495F and R423H-W495H subunits were expressed at a 1:1 ratio. Shown are representative, unsubtracted current traces recorded at pH 7.2 (left) or 5.5 (centre) by pulsing from –90 mV to voltages ranging from <b>−</b>90 to +60 mV in 10 mV increments. Dashed lines indicate the 0 current level. Right: current amplitudes measured at pH 7.2 (squares) or 5.5 (circles) have been plotted <i>versus</i> voltage. Values are provided as mean ± SEM. The continuous line shows a linear regression fit to the pH 7.2 data.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="6"
|
||
data-label-slug="figure-7">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df4/3413486/b10e66459093/tjp0590-1599-f7.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-6"
|
||
role="button"
|
||
data-image-width="480"
|
||
data-image-height="561"
|
||
data-image-alt="Figure 7"
|
||
data-pmc-id="PMC3413486"
|
||
data-figure-id="fig07">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-6"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df4/3413486/5837a1fc8713/tjp0590-1599-f7.gif"
|
||
alt="Figure 7" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="480">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="561">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 7. F448L and R423H subunits have… </p>
|
||
</strong>
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<strong class="figure-label">
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<p> Figure 7. F448L and R423H subunits have similar effects on Kv3.3 channel gating </p>
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<div class="figure-caption-contents"><i> A </i> ,…</div>
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<strong class="figure-label">
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Figure 7. F448L and R423H subunits have similar effects on Kv3.3 channel gating
|
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</strong>
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<div class="figure-caption-contents"><i>A</i>, normalized conductance has been plotted as a function of voltage for wild type Kv3.3 (▪, <i>n</i> = 218) or F448L (•, <i>n</i> = 74) expressed alone and for wild type and F448L expressed at a 1:1 ratio (□, <i>n</i> = 49). Values are provided as mean ± SEM. Data sets were fitted with single Boltzmann functions (continuous lines). Midpoint voltages and slope factors are shown in Table 1. <i>B</i>, current traces were fitted with a single exponential function to estimate τ<sub>act</sub>, which has been plotted <i>versus</i> voltage. Data are shown for wild type (▪) or F448L (•) expressed alone and for wild type and F448L expressed at a 1:1 ratio (□). Values are provided as mean ± SEM (<i>n</i>≥ 25) and differed significantly by one-way ANOVA followed by 2 sample <i>t</i> test, <i>P</i> < 0.05 (*F448L alone and 1:1 ratio differ from wild type; **1:1 differs from F448L alone). <i>C</i>, tail currents were recorded in a high Rb<sup>+</sup> bath solution by pulsing from <b>−</b>90 to +40 mV prior to repolarizing to –65 mV for wild type or F448L expressed alone or for wild type expressed at a 1:1 ratio with F448L as indicated. Representative results are shown. <i>D</i>, tail currents were evoked in high Rb<sup>+</sup> by repolarizing from +40 mV to voltages ranging from <b>−</b>25 to –90 mV. Tail current traces were fitted with a single exponential function to estimate τ<sub>deact</sub>, which has been plotted <i>versus</i> repolarization voltage for wild type (▪) or F448L (•) expressed alone and for wild type and F448L expressed at ratios of 1:0.25 (▿), 1:0.5 (▵) and 1:1 (□). Values are provided as mean ± SEM, <i>n</i> ≥ 25. All τ<sub>deact</sub> values differed significantly from wild type expressed alone, <i>P</i> < 0.05 by Student's <i>t</i> test, except for the 1:0.25 ratio measured at –90 mV. <i>E</i>, tail currents were recorded in a high K<sup>+</sup> bath solution by pulsing from <b>−</b>90 to +40 mV prior to repolarizing to –50 mV for wild type or F448L expressed alone or for wild type expressed at a 1:1 ratio with F448L as indicated. Note change in scale compared to panel <i>C</i>. Representative results are shown. <i>F</i>, tail currents were evoked in high K<sup>+</sup> by repolarizing from +40 mV to voltages ranging from <b>−</b>40 to –80 mV in 10 mV increments. Tail current traces were fitted with a single exponential function to estimate τ<sub>deact</sub>, which has been plotted <i>versus</i> repolarization voltage for wild type (▪) or F448L (•) expressed alone and for wild type and F448L expressed at a 1:1 ratio (□). Values are provided as mean ± SEM, <i>n</i>≥ 9. All τ<sub>deact</sub> values differed significantly from wild type expressed alone, <i>P</i> < 0.00001 by one-way ANOVA followed by 2 sample <i>t</i> test.</div>
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<span class="docsum-authors full-authors">Muona M, Berkovic SF, Dibbens LM, Oliver KL, Maljevic S, Bayly MA, Joensuu T, Canafoglia L, Franceschetti S, Michelucci R, Markkinen S, Heron SE, Hildebrand MS, Andermann E, Andermann F, Gambardella A, Tinuper P, Licchetta L, Scheffer IE, Criscuolo C, Filla A, Ferlazzo E, Ahmad J, Ahmad A, Baykan B, Said E, Topcu M, Riguzzi P, King MD, Ozkara C, Andrade DM, Engelsen BA, Crespel A, Lindenau M, Lohmann E, Saletti V, Massano J, Privitera M, Espay AJ, Kauffmann B, Duchowny M, Møller RS, Straussberg R, Afawi Z, Ben-Zeev B, Samocha KE, Daly MJ, Petrou S, Lerche H, Palotie A, Lehesjoki AE.</span>
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<span class="docsum-journal-citation full-journal-citation">Nat Genet. 2015 Jan;47(1):39-46. doi: 10.1038/ng.3144. Epub 2014 Nov 17.</span>
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Rare Gain-of-Function <em>KCND3</em> Variant Associated with Cerebellar Ataxia, Parkinsonism, Cognitive Dysfunction, and Brain Iron Accumulation.
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Baukrowitz T, Yellen G. Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms. Neuron. 1995;15:951–960.
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aria-label="Dropdown menu for keyword Humans"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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In Vitro Techniques
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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Ion Channel Gating / physiology*
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Mutation
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Protein Subunits / physiology
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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Spinocerebellar Degenerations / physiopathology*
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Xenopus laevis
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</div>
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<div id="substances" class="substances keywords-section">
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<h2 class="title">
|
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Substances
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</h2>
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<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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KCNC3 protein, human
|
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