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Review
. 2015 Aug 19:9:317.
doi: 10.3389/fncel.2015.00317. eCollection 2015.

New insights into the pathogenesis and therapeutics of episodic ataxia type 1

Maria Cristina D'Adamo  1 , Sonia Hasan  1 , Luca Guglielmi  1 , Ilenio Servettini  1 , Marta Cenciarini  1 , Luigi Catacuzzeno  2 , Fabio Franciolini  2
Affiliations
Review

New insights into the pathogenesis and therapeutics of episodic ataxia type 1

Maria Cristina D'Adamo et al. Front Cell Neurosci. .

Abstract

Episodic ataxia type 1 (EA1) is a K(+) channelopathy characterized by a broad spectrum of symptoms. Generally, patients may experience constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with loss of both motor coordination and balance. During attacks additional symptoms may be reported such as vertigo, blurred vision, diplopia, nausea, headache, diaphoresis, clumsiness, stiffening of the body, dysarthric speech, and difficulty in breathing. These episodes may be precipitated by anxiety, emotional stress, fatigue, startle response or sudden postural changes. Epilepsy is overrepresented in EA1. The disease is inherited in an autosomal dominant manner, and genetic analysis of several families has led to the discovery of a number of point mutations in the voltage-dependent K(+) channel gene KCNA1 (Kv1.1), on chromosome 12p13. To date KCNA1 is the only gene known to be associated with EA1. Functional studies have shown that these mutations impair Kv1.1 channel function with variable effects on channel assembly, trafficking and biophysics. Despite the solid evidence obtained on the molecular mechanisms underlying EA1, how these cause dysfunctions within the central and peripheral nervous systems circuitries remains elusive. This review summarizes the main breakthrough findings in EA1, discusses the neurophysiological mechanisms underlying the disease, current therapies, future challenges and opens a window onto the role of Kv1.1 channels in central nervous system (CNS) and peripheral nervous system (PNS) functions.

Keywords: KCNA1; Kv1.1 potassium channel; channelopathy; episodic ataxia type 1; episodic ataxia type 1 therapy; point mutations.

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Figures

Figure 1
Figure 1
KCNA1 mutations identified in episodic ataxia type 1 (EA1) individuals. Cartoon showing the membrane topology of a human Kv1.1 subunit and the positions of the EA1 mutations. Up-dated and adapted from D’Adamo (2010).
See this image and copyright information in PMC

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References

    1. Adelman J. P., Bond C. T., Pessia M., Maylie J. (1995). Episodic ataxia results from voltage-dependent potassium channels with altered functions. Neuron 15, 1449–1454. 10.1016/0896-6273(95)90022-5 - DOI - PubMed
    1. Ambrosini E., Sicca F., Brignone M. S., D’Adamo M. C., Napolitano C., Servettini I., et al. . (2014). Genetically induced dysfunctions of Kir2.1 channels: implications for short QT3 syndrome and autism-epilepsy phenotype. Hum. Mol. Genet. 23, 4875–4886. 10.1093/hmg/ddu201 - DOI - PMC - PubMed
    1. Assaf S. Y., Chung S. H. (1984). Release of endogenous Zn2+ from brain tissue during activity. Nature 308, 734–736. 10.1038/308734a0 - DOI - PubMed
    1. Bain J. R., Mackinnon S. E., Hudson A. R., Wade J., Evans P., Makino A., et al. . (1992). The peripheral nerve allograft in the primate immunosuppressed with Cyclosporin A: I. Histologic and electrophysiologic assessment. Plast. Reconstr. Surg. 90, 1036–1046. 10.1097/00006534-199212000-00015 - DOI - PubMed
    1. Begum R., Kullmann D. M. (2011). “Altered presynaptic spike properties in cerebellar basket cells in a mouse model of episodic ataxia type 1,” Program No. 447.15/E26, 2011 Neuroscience Meeting Planner, (Washington, DC: Society for Neuroscience; ). Available online at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=2773&sKey=2642...