Remifentanil induces l-type ca2+ channel inhibition in human mesenteric arterial smooth muscle cells

Abstract

Remifentanil is known to cause vasodilation at standard anesthetic concentrations. The intracellular mechanisms underlying its vasodilator action may involve the activation of ion channels. The purpose of this study was to examine whether remifentanil inhibits L-type calcium channels (Ca.(L)) and provides dose-dependent effects on L-type calcium channel Ba(2+) currents (I(Ba.L)) in human mesenteric arterial smooth muscle cells. Using the whole-cell patch-clamp method, an in depth analysis of the mechanism of the I(Ba.L) induced by remifentanil was performed in cells which were enzymatically isolated from human mesenteric arterial smooth muscle. Ten millimolars Ba(2+) was used to replace 1.5 mM Ca(2+) to increase the amplitude of the inward current through Ca(2+)channels. L-type calcium channel Ba(2+) was elicited during 50 msec depolarizing test pulses (150 msec duration) to +80 mV (10 mV increments) from a holding potential of -60 mV. The effects of remifentanil on Ca.(L) were observed at the following concentrations: 1.21, 4.84, and 19.4 nmol.L(-1) and were compared with control. Remifentanil produced a concentration-dependent block of I(Ba,L) with IC(50) values of 38.90 +/- 3.96 x 10(-3) micromol.L(-1). The L-type calcium channel blocker, nifedipine, antagonized these remifentanil-induced currents. Remifentanil, at all concentrations, shifted the maximum of the current-voltage relationship in the hyperpolarizing direction of I(Ba.L). Remifentanil significantly inhibits Ca.(L) channels in a concentration-dependent manner in human mesenteric arteriolar smooth muscle cells.