The effects of halothane, enflurane, and isoflurane on calcium current in isolated canine ventricular cells

Abstract

The effects of halothane, enflurane, and isoflurane on voltage-dependent Ca2+ channel current (I(Ca)) were compared in canine ventricular cells by the whole-cell voltage-clamp technique. I(Ca) was elicited in each cell by progressively depolarizing pulses, from -80 or -40 mV to more positive membrane potentials. The peak amplitude and inactivation rate of the inward current were analyzed before, during, and after the external application of equianesthetic concentrations (0.5, 1.0, and 2.0 MAC) of halothane, enflurane, or isoflurane. The concentrations of these agents in the Kreb's solution were as follows (percentage in the gas phase): halothane 0.36, 0.68, and 1.50%; isoflurane 0.50, 1.00, and 1.90%; and enflurane 0.66, 1.36, and 2.39%. Halothane, enflurane, and isoflurane rapidly reduced peak I(Ca) amplitude at all voltages studied, resulting in a depression of the entire current-voltage relationship for I(Ca) activation. This depression was concentration-dependent and completely reversible upon wash-out of the anesthetic agents. Quantitatively, the three anesthetic agents produced a similar inhibition of peak I(Ca) at approximately equianesthetic concentrations. Inactivation of I(Ca) during 200-ms depolarizing pulses was not affected by two lower concentrations of the anesthetic agents, but was accelerated by the highest concentration of enflurane used. These findings suggest that the negative inotropic and chronotropic actions of halothane, enflurane, and isoflurane on the ventricular myocardium are related, at least in part, to their inhibition of I(Ca) at the sarcolemma. However, since all three anesthetic agents depressed I(Ca) amplitude similarly, their quantitatively different effects on cardiac performance are due most likely to differences in actions at other cellular sites.