Distinctive role of K(V)1.1 subunit in the biology and functions of low threshold K+ channels with implications for neurological disease

作者：Ovsepian Saak V^*; LeBerre Marie; Steuber Volker; O'Leary Valerie B; Leibold Christian; Dolly J Oliver

来源：Pharmacology & Therapeutics, 2016, 159: 93-101.

DOI：10.1016/j.pharmthera.2016.01.005

• KCNA1
• Low-threshold potassium channel
• Hetero-tetramer
• Dendrotoxin-K
• Synaptic integration
• Episodic ataxia 1 (EA1)

The diversity of pore-forming subunits of K(V)1 channels (K(V)1.1-K(V)1.8) 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 K(V)1 channels have been linked exclusively to mutations in the KCNA1 gene encoding for the K(V)1.1 subunit. The absence of phenotypes related to irregularities in other subunits, including the prevalent K(V)1.2 subunit of neurons is highly perplexing given that deletion of the corresponding kcna2 gene in mouse models precipitates symptoms reminiscent to those of K(V)1.1 knockouts. Herein, we critically evaluate the molecular and biophysical characteristics of the K(V)1.1 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 insights towards a better understanding of the role of K(V)1.1 in integrative mechanisms of neurons and synaptic functions under normal and disease conditions.

• 出版日期2016-3