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Benign familial neonatal convulsions caused by altered gating of KCNQ2/KCNQ3 potassium channels.

Pasqualina Castaldo, Emanuele Miraglia Del Giudice, Giangennaro Coppola, Antonio Pascotto, Lucio Annunziato, Maurizio Taglialatela

J. Neurosci., 2002 Jan 15 , 22, RC199

The muscarinic-regulated potassium current (M-current), formed by the heteromeric assembly of subunits encoded by the KCNQ2 and KCNQ3 genes, is a primary regulator of neuronal excitability; this regulation is accomplished by impeding repetitive firing and causing spike-frequency adaptation. Mutations in KCNQ2 or KCNQ3 cause benign familial neonatal convulsions (BFNC), a rare autosomal-dominant generalized epilepsy of newborns, by reducing the maximal current carried by the M-channels without affecting ion selectivity or gating properties. Here we show that KCNQ2/KCNQ3 channels carrying a novel BFNC-causing mutation leading to an arginine to tryptophan substitution in the voltage-sensing S4 domain of KCNQ2 subunits (R214W) displayed slower opening and faster closing kinetics and a decreased voltage sensitivity with no concomitant changes in maximal current or plasma membrane expression. These results suggest that mutation-induced gating alterations of the M-current may cause epilepsy in neonates.

http://www.ncbi.nlm.nih.gov/pubmed/11784811