M. Covarrubias et al., ELIMINATION OF RAPID POTASSIUM CHANNEL INACTIVATION BY PHOSPHORYLATION OF THE INACTIVATION GATE, Neuron, 13(6), 1994, pp. 1403-1412
The effect of protein kinase C (PKC) on rapid N-type inactivation of K
+ channels has not been reported previously. We found that PKC specifi
cally eliminates rapid inactivation of a cloned human A-type K+ channe
l (hKv3.4), converting this channel from a rapidly inactivating A type
to a noninactivating delayed rectifier type. Biochemical analysis sho
wed that the N-terminal domain of hKv3.4 is phosphorylated in vitro by
PKC, and mutagenesis experiments revealed that two serines within the
inactivation gate at the N-terminus are sites of direct PKC action. M
oreover, mutating one of these serines to aspartic acid mimics the act
ion of PKC. Serine phosphorylation may thus prevent rapid inactivation
by shielding basic residues known to be critical to the function of t
he inactivation gate. The regulatory mechanism reported here may have
substantial effects on signal coding in the nervous system.