The Ca2+ channel inhibitor efonidipine decreases voltage-dependent K+ channel activity in rabbit coronary arterial smooth muscle cells

Abstract

The effect of efonidipine, a commercially available antihypertensive drug and Ca2+ channel inhibitor, on voltage-dependent K+ (Kv) channels was studied in freshly isolated rabbit coronary arterial smooth muscle cells using the whole-cell patch clamp technique. The amplitude of Kv current was decreased by application of efonidipine in a dose-dependent manner, with IC50 of 026 mu M and a Hill coefficient of 0.91, which suggests 1:1 binding stoichiometry. Efonidipine did not affect voltage-dependent activation of the Kv channel, but shifted the inactivation curve by -8.87 my. The inhibitory effect of efonidipine was not significantly changed by depletion of extracellular Ca2+ or intracellular ATP, which indicated no involvement of the Ca2+ channel or intracellular protein kinase-dependent cascades. We conclude that efonidipine dose-dependently inhibits Kv current in a phosphorylation- and Ca2+ channel-independent manner. (C) 2013 Elsevier Inc. All rights reserved.