Alternative splicing of KCNQ2 potassium channel transcripts contributes tothe functional diversify of M-currents

1. The region of alternative splicing in the KCNQ2 potassium channel gene w as determined by RNase protection analysis of KCNQ2 mRNA transcripts. 2. Systematic analysis of KCNQ2 alternative splice variant expression in ra t superior cervical ganglia revealed multiple variant isoforms. 3. One class of KCNQ2 splice variants, those that contained exon 15a, was f ound to have significantly different kinetics to those of the other isoform s. These transcripts encoded channel subunits that, when co-expressed with the KCNQ3 subunit, activated and deactivated approximately 2.5 times more s lowly than other isoforms. Deletion of exon 15a in these isoforms produced a reversion to the faster kinetics. 4. Comparison of the kinetic properties of the cloned channel splice varian ts with those of the native M-current suggests that alternative splicing of the KCNQ2 gene may contribute to the variation in M-current kinetics seen in vivo.