Differential effects of etomidate, propofol, and midazolam on calcium and potassium channel currents in canine myocardial cells

Abstract

Background: Intravenous anesthetics etomidate, propofol, and midazolam produce negative inotropic effects of various degrees. The mechanism underlying these differences is largely unknown. Methods: The effects of intravenous anesthetics on L-type Ca 2, transient outward and inward- rectifier K + channel currents (I(Ca), IK(to) and IK 1) were compared in canine ventricular cells using the whole-cell voltage-clamp technique, I(Ca) and I(K) were elicited by progressively depolarizing cells from 40 to +40 mV, and from 90 to +60 mV, respectively. The peak amplitude and time-dependent inactivation rate of I(Ca) and I(K) were measured before, during, and after the administration of equimolar concentrations (5, 30, or 60 μM) of etomidate, propofol, or midazolam. Results: Exposure to etomidate, propofol, and midazolam produced a concentration-dependent inhibition of I(Ca). Midazolam was the most potent intravenous anesthetic; at 60 μM, etomidate, propofol, and midazolam decreased peak I(Ca) by 16 ± 4% (mean ± SEM), 33 ± 5%, and 47 ± 5%, respectively. Etomidate, propofol, and midazolam given in a 60-μM concentration decreased IK(to) by 8 ± 3%, 9 ± 2%, and 23 ± 3%, respectively. IK 1 was decreased by 60 μM etomidate and midazolam by 20 ± 6% and 14% ± 5%, respectively. Propofol had no effect on IK 1. Conclusions: At equimolar concentrations, intravenous anesthetics decreased the peak I(Ca), I(Kto), and I(K1) with various degrees of potency. Effects of anesthetics on I(Ca), were significantly greater compared with their effects on K + currents. These findings suggest that the negative inotropic actions of etomidate, propofol, and midazolam are related, at least in part, to decreased I(Ca). Some effects, such as I(K) inhibition, may partially antagonize effects of decreased I(Ca). Induced, the final effect of these intravenous anesthetics on myocardium will be the sum of these and other sarcolemmal and intracellular effects.