title: Distinctive role of KV1.1 subunit in the biology and functions of low threshold K(+) channels with implications for neurological disease.
abstract: 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 deletion of the corresponding kcna2 gene in mouse models precipitates 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 insights towards a better understanding of the role of KV1.1 in integrative mechanisms of neurons and synaptic functions under normal and disease conditions.
authors.affiliation: Institute of Bio-Medical Imaging at Helmholtz Zentrum Munich, Neuherberg, Germany; International Centre for Neurotherapeutics, Dublin City University, Dublin, Ireland. Electronic address: saak.ovsepian@gmail.com.
authors.forename: Saak V
authors.initials: SV
authors.lastname: Ovsepian
authors.affiliation: National Centre for Biomedical Engineering, National University of Ireland, Galway, Ireland.
authors.forename: Marie
authors.initials: M
authors.lastname: LeBerre
authors.affiliation: Science and Technology Research Institute, University of Hertfordshire, United Kingdom.
authors.forename: Volker
authors.initials: V
authors.lastname: Steuber
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum Munich, Neuherberg, Germany.
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Leary
authors.affiliation: Department Biology, Ludwig II Maximilians University Munich, Martinsried, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Leibold
authors.affiliation: International Centre for Neurotherapeutics, Dublin City University, Dublin, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: Oliver Dolly
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology; D001921:Brain / Q000378:metabolism; D006801:Humans; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D020385:Myokymia / Q000235:genetics / Q000503:physiopathology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D021122:Protein Subunits; D051662:Kv1.1 Potassium Channel
keywords: Dendrotoxin-K; Episodic ataxia 1 (EA1); Hetero-tetramer; KCNA1; Low-threshold potassium channel; Synaptic integration