Abstract
Propofol is a widely used intravenous anesthetic, which is known to affect cardiac functions. Cardiac effects may be caused by direct actions on ion channels of the heart. While effects of propofol on several ion channels have been studied at the whole cell and single-channel levels, its effects, if any, on anion currents have yet to be examined. Effects of propofol on Ca2+-activated Cl-current (Icl(ca)) were investigated in single myocytes isolated from rabbit ventricles by the whole-cell patch clamp technique at 36℃.Icl(ca) was activated by perfusing internal solutions with 0.1 µM free Ca2+ in the absence and presence of 10 mM internal Na+, eliciting Ica-dependent and -independent component, respectively. By the application of propofol (0.1-300 µM), Ica-independent Icl(ca) was strongly inhibited in a dose-dependent manner with an IC50 of about 5 µM. The blocking effects of propofol were voltage independent. On the other hand, the Ica-dependent component of Icl(ca) was little affected by propofol at concentrations of up to 50 µM. The outward Na+/Ca2+ exchanger current was also blocked by application of 5 µM propofol. We conclude that propofol inhibits cardiac Icl(ca) in rabbit ventricular myocytes, mainly the Ica-independent component, at therapeutic concentrations. The inhibition may be due to block of a
reverse mode of Na+/Ca2+ exchange current.