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The Journal of Neuroscience, 2002, 22:RC199:1-6

RAPID COMMUNICATION
Benign Familial Neonatal Convulsions Caused by Altered Gating of KCNQ2/KCNQ3 Potassium Channels

Pasqualina Castaldo¹, Emanuele Miraglia del Giudice², Giangennaro Coppola³, Antonio Pascotto³, Lucio Annunziato¹, and Maurizio Taglialatela¹

¹ Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, 80131 Naples, Italy, and ² Department of Pediatrics and ³ Chair of Child Neuropsychiatry, Second University of Naples, 80131 Naples, Italy

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.

Key words: benign familial neonatal convulsions; BFNC; muscarinic regulated potassium current; M-current; potassium channel gating; S₄ voltage sensor; KCNQ2; epilepsy

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Copyright © Society for Neuroscience  0270-6474//$05.00/0

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