Modulation of cardiac calcium channels by propofol.

BACKGROUND

Propofol elicits a rapid depression of transsarcolemmal Ca2+ influx and myocardial contractility. However, the mechanism underlying this action has not been well described. The present study was designed to test the hypothesis that propofol acts as an antagonist of L-type calcium channels.

METHODS

Experiments monitored effects of propofol on (1) the binding of [3H]nitrendipine (a 1,4-dihydropyridine calcium channel antagonist) to rat myocardial membranes; (2) L-type calcium current (ICa,L) as determined using whole-cell patch-clamp techniques in intact rat cardiomyocytes; and (3) myocardial contractility as examined in isolated rat papillary muscle.

RESULTS

Propofol, in concentrations as low as 6 microM, increased the apparent dissociation constant (Kd) for [3H]nitrendipine without affecting binding-site density (Bmax). This decrease in dihydropyridine-binding affinity was associated with a depressed ICa,L in cardiomyocytes and diminished myocardial contractility. Other experiments showed that etomidate has no effect on [3H]nitrendipine binding, whereas ketamine enhances dihydropyridine binding.

CONCLUSION

Results suggest that propofol may inhibit cardiac L-type calcium current by interacting with the dihydropyridine-binding site.