Channelpedia

PubMed 20940059


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ1 , KCNQ2 , KCNQ3 , KCNQ5 , Kv7.1 , Kv7.2 , Kv7.3 , Kv7.5



Title: Made for "anchorin": Kv7.2/7.3 (KCNQ2/KCNQ3) channels and the modulation of neuronal excitability in vertebrate axons.

Authors: Edward C Cooper

Journal, date & volume: Semin. Cell Dev. Biol., 2011 Apr , 22, 185-92

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20940059


Abstract
Kv7.2 and Kv7.3 (encoded by KCNQ2 and KCNQ3) are homologous subunits forming a widely expressed neuronal voltage-gated K(+) (Kv) channel. Hypomorphic mutations in either KCNQ2 or KCNQ3 cause a highly penetrant, though transient, human phenotype-epilepsy during the first months of life. Some KCNQ2 mutations also cause involuntary muscle rippling, or myokymia, which is indicative of motoneuron axon hyperexcitability. Kv7.2 and Kv7.3 are concentrated at axonal initial segments (AISs), and at nodes of Ranvier in the central and peripheral nervous system. Kv7.2 and Kv7.3 share a novel ∼80 residue C-terminal domain bearing an "anchor" motif, which interacts with ankyrin-G and is required for channel AIS (and likely, nodal) localization. This domain includes the sequence IAEGES/TDTD, which is analogous (not homologous) to the ankyrin-G interaction motif of voltage-gated Na(+) (Na(V)) channels. The KCNQ subfamily is evolutionarily ancient, with two genes (KCNQ1 and KCNQ5) persisting as orthologues in extant bilaterian animals from worm to man. However, KCNQ2 and KCNQ3 arose much more recently, in the interval between the divergence of extant jawless and jawed vertebrates. This is precisely the interval during which myelin and saltatory conduction evolved. The natural selection for KCNQ2 and KCNQ3 appears to hinge on these subunits' unique ability to be coordinately localized with Na(V) channels by ankyrin-G, and the resulting enhancement in the reliability of neuronal excitability.