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XB-ART-38
Neurobiol Dis October 1, 2006; 24 (1): 194-201.
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Subthreshold changes of voltage-dependent activation of the K(V)7.2 channel in neonatal epilepsy.

Hunter J , Maljevic S , Shankar A , Siegel A , Weissman B , Holt P , Olson L , Lerche H , Escayg A .


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.

PubMed ID: 16916607
Article link: Neurobiol Dis
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: chrna4 kcnq2 kcnq3

Disease Ontology terms: benign neonatal seizures