Alternative splicing of KCNQ2 potassium channel transcripts contributes to the functional diversity of M-currents

1. The region of alternative splicing in the KCNQ2 potassium channel gene was determined by RNase protection analysis of KCNQ2 mRNA transcripts. 2. Systematic analysis of KCNQ2 alternative splice variant expression in rat superior cervical ganglia revealed multiple variant isoforms. 3. One class of KCNQ2 splice variants, those that contained exon 15a, was found to have significantly different kinetics to those of the other isoforms. These transcripts encoded channel subunits that, when co-expressed with the KCNQ3 subunit, activated and deactivated approximately 2.5 times more slowly 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 variants 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.