MODULATION OF CARDIAC CALCIUM CHANNELS BY PROPOFOL

Background: Propofol elicits a rapid depression of transsarcolemmal Ca 2+ influx and myocardial contractility. However, the mechanism underly ing this action has not been well described. The present study was des igned to test the hypothesis that propofol acts as an antagonist of L- type calcium channels. Methods: Experiments monitored effects of propo fol on (1) the binding of [H-3]nitrendipine (a 1,4-dihydropyridine cal cium channel antagonist) to rat myocardial membranes; (2) L-type calci um current (I-Ca,I-L) as determined using whole-cell patch-clamp techn iques in intact rat cardiomyocytes; and (3) myocardial contractility a s examined in isolated rat papillary muscle. Results: Propofol, in con centrations as low as 6 mu M, increased the apparent dissociation cons tant (K-d) for [H-3]nitrendipine without affecting binding-site densit y (B-max). This decrease in dihydropyridine-binding affinity was assoc iated with a depressed I-Ca,I-L in cardiomyocytes and diminished myoca rdial contractility. Other experiments showed that etomidate has no ef fect on [H-3]nitrendipine binding, whereas ketamine enhances dihydropy ridine binding. Conclusion: Results suggest that propofol may inhibit cardiac L-type calcium current by interacting with the dihydropyridine -binding site.