Effects of halothane and isoflurane on calcium and potassium channel currents in canine coronary arterial cells

Abstract

The effects of halothane (0.75% and 1.5%) and isoflurane (2.6%) on macroscopic Ca2+ and K+ channel currents (I(Ca) and I(K), respectively) were investigated in voltage-clamped vascular muscle cells from the canine coronary artery. Single coronary arterial cells were dialyzed with K+ glutamate solution and superfused with Tyrode's solution for measurement of I(K) (n = 45). Stepwise depolarization from a holding potential of -60 mV to beyond -30 mV elicited an outward, slowly inactivating I(K) that had a macroscopic slope conductance of 18 nS. I(K) was reduced 75% by 10 mM 4- aminopyridine, a K+ channel antagonist. Compared to 4-aminopyridine, halothane at 0.75% and 1.5% reduced peak I(K) amplitude only by 14 ± 2% and 36 ± 3%, respectively. At approximately equianesthetic concentrations, 2.6% isoflurane suppressed I(K) less than did 1.5% halothane, reducing peak amplitude by 15 ± 3%. In other sets of experiments, cells were dialyzed with 120 Cs+-glutamate solution and superfused with 10 mM BaCl2 or CaCl2 solutions to isolate I(Ca) (n = 39) pharmacologically. Under these conditions, progressive depolarizing steps from -60 mV elicited a small inward current, which was potentiated 3.4-fold by equimolar substitution of Ba2+ for Ca2+ in the external solution and was blocked by 1 μM nifedipine. This inward current, which resembled L-type I(Ca), was blocked 37 ± 4% and 70 ± 4% in the presence of 0.75% and 1.5% halothane, respectively. Isoflurane (2.6%) also decreased I(Ca) by 55 ± 5%. It appears that while halothane and isoflurane suppress both I(K) and I(Ca), these anesthetics preferentially reduce I(Ca). Also, at equianesthetic concentrations, halothane (1.5%) appears more potent than isoflurane (2.6%) in suppressing ionic currents in the coronary arterial cells. The significantly greater suppression of I(K) and I(Ca) by 1.5% halothane than 2.6% isoflurane may contribute to the more predominant halothane-induced coronary dilation by halothane. Thus, in the coronary artery, which relies on Ca2+ entry for vascular muscle activation, the reduced Ca2+ influx may represent one of the mechanisms by which volatile anesthetics induce vasodilation.