Calcium channel inhibitor, verapamil, inhibits the voltage-dependent K+ channels in rabbit coronary smooth muscle cells.
We investigated the effect of the phenylalkylamine Ca(2+) channel inhibitor verapamil on voltage-dependent K(+) (Kv) channels in rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Verapamil reduced the Kv current amplitude in a concentration-dependent manner. The apparent K(d) value for Kv channel inhibition was 0.82 microM. Although verapamil had no effect on the activation kinetics, it accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation by verapamil were 2.20+/-0.02 microM(-1) s(-1), and 1.79+/-0.26 s(-1), respectively. The steady-state activation and inactivation curves were unaffected by verapamil. The application of train pulses increased the verapamil-induced Kv channel inhibition. Furthermore, verapamil increased the recovery time constant, suggesting that the inhibitory effect of this agent was use-dependent. The inhibitory effect of verapamil was not affected by intracellular and extracellular Ca(2+)-free conditions. Another Ca(2+) channel inhibitor, nifedipine (10 microM) did not affect the Kv current, and did not alter the inhibitory effect of verapamil. Based on these results, we concluded that verapamil inhibited Kv current in a state-, time-, and use-dependent manner, independent of Ca(2+) channel inhibition.
Ko
Eun A
EA
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Biomarker Medical Research Center, FIRST Mitochondrial Research Group, Inje University, Busan, Korea.
Park
Won Sun
WS
Son
Youn Kyoung
YK
Ko
Jae-Hong
JH
Choi
Tae-Hoon
TH
Jung
In Duk
ID
Park
Yeong-Min
YM
Hong
Da Hye
DH
Kim
Nari
N
Han
Jin
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D003331:Coronary Vessels; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D014700:Verapamil; D002118:Calcium