EVIDENCE FOR AN INTERACTION OF HALOTHANE WITH THE L-TYPE CA-2+ CHANNEL IN HUMAN MYOCARDIUM

Citation
U. Schmidt et al., EVIDENCE FOR AN INTERACTION OF HALOTHANE WITH THE L-TYPE CA-2+ CHANNEL IN HUMAN MYOCARDIUM, Anesthesiology, 79(2), 1993, pp. 332-339
Citations number
21
Categorie Soggetti
Anesthesiology
Journal title
ISSN journal
00033022
Volume
79
Issue
2
Year of publication
1993
Pages
332 - 339
Database
ISI
SICI code
0003-3022(1993)79:2<332:EFAIOH>2.0.ZU;2-8
Abstract
Background. The present study was aimed at investigating the underlyin g mechanisms for the cardiac depressant effect of halothane. To test t he hypothesis, whether there is an interaction of halothane with the L -type Ca2+ channels in human myocardium and whether this interaction h as functional consequences for force generation in the human myocardiu m, effects of halothane were studied in human myocardial membranes and isolated cardiac preparations. Methods: The experiments were performe d on isolated, electrically driven ventricular preparations (1 Hz, 37- degrees-C) and cardiac membranes with radioligand binding experiments using H-3-PN 200-110. Myocardium from human failing and non-failing he arts was obtained at cardiac surgery. Results. Halothane produced a ne gative inotropic effect, which was similar in nonfailing and failing m yocardium. Halothane shifted the concentration-response curve for the positive inotropic effect of the L-type Ca2+ channel agonist BayK 8644 to the right. The density of dihydropyridine receptors as judged from H-3-PN 200-110 radioligand binding experiments was similar in nonfail ing and failing myocardium, whereas the density of beta-adrenoceptors was reduced. Halothane concentration dependently reduced the binding o f H-3-PN 200-110, an antagonist at the 1,4 dihydropyridine receptor si te of the Ca2+ channel, to myocardial membranes. Furthermore, halothan e produced a rightward shift of the competition curve of BayK 8644 for binding of H-3-PN 200-110 to cardiac membranes.Conclusions. in human ventricular myocardium, halothane exhibits an interaction with the L-t ype Ca2+ channel by interfering with its dihydropyridine binding sites . This may explain, at least in part, the observed negative inotropic effect of this agent and could hypothetically play a general role in i ts anesthetic effects.