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
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.