TY - JOUR
T1 - Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate
AU - Covarrubias, Manuel
AU - Wei, Aguan
AU - Salkoff, Lawrence
AU - Vyas, Tapan B.
N1 - Funding Information:
We than k Mr. C. Choe for valuable technical assistance and Drs. P. De Weer and R. Horn for critical comments on earlier versions of this manuscript. We also thank Drs. S. Slater and C. Stubbs (Jefferson Medical College) for providing purified brain PKC and for testing phosphorylation in vitro of the Raw3 peptide and Dr. R. Sorensen (Jefferson Medical College) for purifying Raw3 N-terminal peptide, hKv3.4 clone was provided by Dr. B. Rudy (New York University Medical Center), and Raw3 N-terminal peptide was a gift from Dr. R. W. Aldrich (Stanford University). We thank them for supplying these materials. This work was supported by NIH grants NS32337 (M. C.) and NS24785 (L. S.) and in part by NIAAA program project grant AA07186. T. B. V. was supported by PHS training grant AA07463. All correspondence should be addressed to M. C.
PY - 1994/12
Y1 - 1994/12
N2 - The effect of protein kinase C (PKC) on rapid N-type inactivation of K+ channels has not been reported previously. We found that PKC specifically eliminates rapid inactivation of a cloned human A-type K+ channel (hKv3.4), converting this channel from a rapidly inactivating A type to a noninactivating delayed rectifier type. Biochemical analysis showed 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. Moreover, mutating one of these serines to aspartic acid mimics the action of PKC. Serine phosphorylation may thus prevent rapid inactivation by shielding basic residues known to be critical to the function of the inactivation gate. The regulatory mechanism reported here may have substantial effects on signal coding in the nervous system.
AB - The effect of protein kinase C (PKC) on rapid N-type inactivation of K+ channels has not been reported previously. We found that PKC specifically eliminates rapid inactivation of a cloned human A-type K+ channel (hKv3.4), converting this channel from a rapidly inactivating A type to a noninactivating delayed rectifier type. Biochemical analysis showed 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. Moreover, mutating one of these serines to aspartic acid mimics the action of PKC. Serine phosphorylation may thus prevent rapid inactivation by shielding basic residues known to be critical to the function of the inactivation gate. The regulatory mechanism reported here may have substantial effects on signal coding in the nervous system.
UR - http://www.scopus.com/inward/record.url?scp=0028605349&partnerID=8YFLogxK
U2 - 10.1016/0896-6273(94)90425-1
DO - 10.1016/0896-6273(94)90425-1
M3 - Article
C2 - 7993631
AN - SCOPUS:0028605349
SN - 0896-6273
VL - 13
SP - 1403
EP - 1412
JO - Neuron
JF - Neuron
IS - 6
ER -