PuSH - Publikationsserver des Helmholtz Zentrums München: Distinctive role of KV1.1 subunit in the biology and functions of low threshold K<sup>+</sup> channels with implications for neurological disease.

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Ovsepian, S.V. ; LeBerre, M.* ; Steuber, V.* ; O'Leary, V.B. ; Leibold, C.* ; Dolly, J.O.*

Distinctive role of KV1.1 subunit in the biology and functions of low threshold K⁺ channels with implications for neurological disease.

Pharmacol. Ther. 159, 93-101 (2016)

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The diversity of pore-forming subunits of KV1 channels (KV1.1-KV1.8) affords their physiological versatility and predicts a range of functional impairments resulting from genetic aberrations. Curiously, identified so far human neurological conditions associated with dysfunctions of KV1 channels have been linked exclusively to mutations in the KCNA1 gene encoding for the KV1.1 subunit. The absence of phenotypes related to irregularities in other subunits, including the prevalent KV1.2 subunit of neurons is highly perplexing given that deletions of corresponding kcna2 gene in mouse models precipitate symptoms reminiscent to those of KV1.1 knockouts. Herein, we critically evaluate the molecular and biophysical characteristics of the KV1.1 protein in comparison with others and discuss their role in the greater penetrance of KCNA1 mutations in humans leading to the neurological signs of episodic ataxia type 1 (EA1). Future research and interpretation of emerging data should afford new insight towards a better understanding of the role of KV1.1 in integrative mechanisms of neurons and synaptic functions under normal and disease conditions.

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PuSH - Publikationsserver des Helmholtz Zentrums München

Distinctive role of KV1.1 subunit in the biology and functions of low threshold K+ channels with implications for neurological disease.

Distinctive role of KV1.1 subunit in the biology and functions of low threshold K⁺ channels with implications for neurological disease.