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

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 Ca2+, transient outward and inward-rectifier K+ channel currents (I-Ca, I-Kto, and IK1) 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 mu M) of etomidate, propofol, or midazolam. Results: Exposure to etomidate, propofol, and midazolnm produced a concentration-dependent inhibition of I-Ca. Midazolam was the most potent intraveuous anesthetic; at 60 mu M, 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-mu M concentration decreased IKto by 8 +/- 3%, 9 +/- 2%, and 23 +/- 3%, respectively. IK1 was decreased by 60 mu M etomidate and midazolam by 20 +/- 6% and 14% +/- 5%, respectively. Propofol had no effect on IK1. 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. Indeed, the final effect of these intravenous anesthetics on myocardium will be the sum of these and other sarcalemmal and intracellular effects.