KChIP2b modulates the affinity and use-dependent block of Kv4.3 by nifedipine.
Rapidly activating Kv4 voltage-gated ion channels are found in heart, brain, and diverse other tissues including colon and uterus. Kv4.3 can co-assemble with KChIP ancillary subunits, which modify kinetic behavior. We examined the affinity and use dependence of nifedipine block on Kv4.3 and its modulation by KChIP2b. Nifedipine (150 microM) reduced peak Kv4.3 current approximately 50%, but Kv4.3/KChIP2b current only approximately 27%. Nifedipine produced a very rapid component of open channel block in both Kv4.3 and Kv4.3/KChIP2b. However, recovery from the blocked/inactivated state was strongly sensitive to KChIP2b. Kv4.3 Thalf,recovery was slowed significantly by nifedipine (120.0+/-12.4 ms vs. 213.1+/-18.2 ms), whereas KChIP2b eliminated nifedipine's effect on recovery: Kv4.3/KChIP2b Thalf,recovery was 45.3+/-7.2 ms (control) and 47.8+/-8.2 ms (nifedipine). Consequently, Kv4.3 exhibited use-dependent nifedipine block in response to a series of depolarizing pulses which was abolished by KChIP2b. KChIPs alter drug affinity and use dependence of Kv4.3.
Bett
Glenna C L
GC
Center for Cellular and Systems Electrophysiology, Department of Gynecology and Obstetrics, School of Medicine and Biomedical Sciences, 124 Sherman Hall, State University of New York at Buffalo, Buffalo, NY 14214-300, USA.
Morales
Michael J
MJ
Strauss
Harold C
HC
Rasmusson
Randall L
RL
D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D015640:Ion Channel Gating / Q000502:physiology*; D051605:Kv Channel-Interacting Proteins / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D011485:Protein Binding; D051672:Shal Potassium Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology*; D014982:Xenopus laevis
D002121:Calcium Channel Blockers; D051605:Kv Channel-Interacting Proteins; D051672:Shal Potassium Channels; D009543:Nifedipine