Halothane decreases calcium channel antagonist binding to cardiac membranes.
The effect of halothane concentration on the binding of the calcium antagonist, [3H] nitrendipine (3HNTP), to rat and rabbit heart membranes was examined in vitro because it has been hypothesized that one mechanism by which halothane depresses cardiac contractility is by interfering with Ca2+ channel function. Membranes were incubated for 90 minutes in a closed system with 3HNTP and increasing concentrations of halothane. The amount of 3HNTP bound to membranes was quantified by radioligand binding technique and liquid scintillation counting. It was found in both the rat and rabbit cardiac membranes that halothane (0.4-2.0%) caused a dose-dependent decrease in specific 3HNTP binding (P less than 0.0001). The decrease in 3HNTP binding caused by halothane was also found to be reversible. These results indicate that halothane interferes with one property of the Ca2+ channel and suggest that this may be one possible mechanism for the negative inotropic action of halothane.
Blanck
T J
TJ
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland 21205.
Runge
S
S
Stevenson
R L
RL
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism*; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
D015220:Calcium Channels; D011978:Receptors, Nicotinic; D009568:Nitrendipine; D006221:Halothane