Effects of etomidate on whole-cell and single L-type calcium channel currents in guineapig isolated ventricular myocytes

Abstract

We have investigated the effects of etomidate 4.4 mumol litre-1, 1.0 mg litre-1 and 27.4 mumol litre-1, 6.25 mg litre-1 on whole-cell and single L-type calcium channel currents in myocytes from guineapig ventricles. For whole-cell recordings, the cells were voltage-clamped and step depolarizations were applied from holding potential of -40 mV to various potentials to elicit L-type calcium currents. Peak calcium currents were decreased significantly by both low and high concentrations of etomidate. Ethanol in the same concentration with the highest etomidate solution (1.1 mmol litre-1) had no significant effect on calcium currents. When single calcium channel activity was investigated, the high concentration of etomidate significantly decreased the open probability of the channel with little or no effect on channel conductance. Mean closed time was increased significantly, caused apparently by prolongation of the slower of two exponential components fitted to histograms of the closed times. The mean open time was virtually unaffected. The low concentration of etomidate did not significantly affect single channel kinetics. These results showed that etomidate decreased L-type calcium current by altering the kinetics of the channel to favour the closed state without any significant change in conductance. However, compared with other anaesthetics which were investigated previously in our laboratory, the overall effect on calcium current appeared to be small.