FUNCTIONAL EXPRESSION OF 2 KVLQT1-RELATED POTASSIUM CHANNELS RESPONSIBLE FOR AN INHERITED IDIOPATHIC EPILEPSY

Benign familial neonatal convulsions (BFNC), a class of idiopathic gen eralized epilepsy, is an autosomal dominantly inherited disorder of ne wborns. BFNC has been linked to mutations in two putative K+ channel g enes, KCNQ2 and KCNQ3, Amino acid sequence comparison reveals that bot h genes share strong homology to KvLQT1, the potassium channel encoded by KCHQ1, which is responsible for over 50% of inherited long QT synd rome. Here we describe the cloning, functional expression, and charact erization of K+ channels encoded by KCNQ2 and KCNQ3 cDNAs, Individuall y, expression of KCNQ2 or KCNQ3 in Xenopus oocytes elicits voltage-gat ed, rapidly activating K+-selective currents similar to KCNQ1, However , unlike KCNQ1, KCNQ2 and KCNQ3 currents are not augmented by coexpres sion with the KCNQ1 beta subunit, KCNE1 (minK, IsK). Northern blot ana lyses reveal that KCNQ2 and KCNQ3 exhibit similar expression patterns in different regions within the brain. Interestingly, coexpression of KCNQ2 and KCNQ3 results in a substantial synergistic increase in curre nt amplitude. Coexpression of KCNE1 with the two channels strongly sup pressed current amplitude and slowed kinetics of activation. The pharm acological and biophysical properties of the K+ currents observed in t he coinjected oocytes differ somewhat from those observed after inject ing either KCNQ2 or KCNQ3 by itself. The functional interaction betwee n KCNQ2 and KCNQ3 provides a framework for understanding how mutations in either channel can cause a form of idiopathic generalized epilepsy .