Propofol is a widely used intravenous general anesthetic. The negative inotropic effect of propofol has been best explained by inhibition of the L-type Ca2+ current (ICa). Using guinea-pig cardiac preparations, however, we found that the propofol concentration producing a 50% decrease in force of contraction was more than 10 times higher than that producing a 50% inhibition of ICa, implying that a compensatory mechanism may be present to counteract the negative inotropic effect associated with the ICa inhibition. Consistent with ICa inhibition, propofol produced a shortening of action potential duration (APD) in single cardiomyocytes. Yet, the concentrations necessary to shorten APD were greater than that for 50% inhibition of ICa. This was associated with the potent and effective inhibition of the slowly activating component of the delayed rectifier K+ current (IKs). Thus, the IKs blockade with propofol may counterbalance the APD shortening evoked by its ICa inhibition. Taken together, the negative inotropic effect of propofol is detectable only at supratherapeutic concentrations. At clinically relevant concentrations, the action potential prolongation mechanism due to IKs inhibition appears to alleviate the reduction in transsarcolemmal Ca2+ influx through L-type Ca2+ channels, which may help to counteract the net negative inotropism of propofol.
The Japanese Pharmacological Society 2009