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.


CONCLUSIONS
Results suggest that propofol may inhibit cardiac L-type calcium current by interacting with the dihydropyridine-binding site.
Zhou
W
W
Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
Fontenot
H J
HJ
Liu
S
S
Kennedy
R H
RH
D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003864:Depression, Chemical; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism; D015742:Propofol / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002316:Cardiotonic Agents; D014316:Tritium; D009568:Nitrendipine; D015742:Propofol