Referenced in: none

Automatically associated channels: Kv7.2 , Kv7.3 , Slo1

Title: Subthreshold changes of voltage-dependent activation of the K(V)7.2 channel in neonatal epilepsy.

Authors: Jessica Hunter, Snezana Maljevic, Anupama Shankar, Anne Siegel, Barbara Weissman, Philip Holt, Larry Olson, Holger Lerche, Andrew Escayg

Journal, date & volume: Neurobiol. Dis., 2006 Oct , 24, 194-201

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16916607

Abstract
Benign familial neonatal convulsions (BFNC) is an epileptic disorder caused by dominant mutations in the genes KCNQ2 and KCNQ3 encoding the K+ channels K(V)7.2 and K(V)7.3. We identified two novel KCNQ2 mutations in two BFNC families. One mutation predicted a truncated protein (S247X) that lacks the channel's pore region, the other resulted in the amino acid substitution S122L in the S2 segment of K(V)7.2. In comparison to wild-type (WT) K(V)7.2, functional analysis of S122L mutant channels in Xenopus oocytes revealed a significant positive shift and increased slope of the activation curve leading to significant current reduction in the subthreshold range of an action potential (75% reduction at -50 mV). Our results establish an important role of the K(V)7.2 S2 segment in voltage-dependent channel gating and demonstrate in a human disease that subthreshold voltages are likely to represent the physiologically relevant range for this K+ channel to regulate neuronal firing.