Kinetic properties of Kv4.3 and their modulation by KChIP2b.
KChIPs are a family of Kv4 K(+) channel ancillary subunits whose effects usually include slowing of inactivation, speeding of recovery from inactivation, and increasing channel surface expression. We compared the effects of the 270 amino acid KChIP2b on Kv4.3 and a Kv4.3 inner pore mutant [V(399, 401)I]. Kv4.3 showed fast inactivation with a bi-exponential time course in which the fast time constant predominated. KChIP2b expressed with wild-type Kv4.3 slowed the fast time constant of inactivation; however, the overall rate of inactivation was faster due to reduction of the contribution of the slow inactivation phase. Introduction of [V(399, 401)I] slowed both time constants of inactivation less than 2-fold. Inactivation was incomplete after 20s pulse durations. Co-expression of KChIP2b with Kv4.3 [V(399, 401)I] slowed inactivation dramatically. KChIP2b increased the rate of recovery from inactivation 7.6-fold in the wild-type channel and 5.7-fold in Kv4.3 [V(399,401)I]. These data suggest that inner pore structure is an important factor in the modulatory effects of KChIP2b on Kv4.3 K(+) channels.
Wang
Shimin
S
Department of Physiology and Biophysics, University at Buffalo-SUNY, NY 14214, Buffalo, USA.
Patel
Sangita P
SP
Qu
Yujie
Y
Hua
Ping
P
Strauss
Harold C
HC
Morales
Michael J
MJ
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D018076:DNA, Complementary; D007700:Kinetics; D051605:Kv Channel-Interacting Proteins; D008564:Membrane Potentials; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D051672:Shal Potassium Channels; D013329:Structure-Activity Relationship; D014981:Xenopus
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; C497023:Kcnd3 protein, rat; C496758:Kcnip2 protein, rat; D051605:Kv Channel-Interacting Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels