The peripheral, high affinity benzodiazepine binding site is not coupled to the cardiac Ca2+ channel.
Ro 5-4864, the prototype ligand of the peripheral benzodiazepine binding site caused a decrease of the action potential duration in isolated guinea-pig cardiac myocytes. Voltage-clamp experiments showed that, at concentrations below 3 X 10(-6) M, Ro 5-4864 caused a parallel outward shift of the membrane current elicited by depolarization to + 10 mV from a holding potential of -50 mV. The peak inward Ca2+ current (ICa) and the inwardly rectifying K+ current were not affected. ICa was reduced by Ro 5-4864 at concentrations above 3 X 10(-6) M. At these concentrations, Ro 5-4864 also caused a negative inotropic effect in isolated guinea-pig papillary muscles, reduced K+ depolarization-induced contractures of the isolated rat aorta and inhibited [3H]nitrendipine binding to guinea-pig cardiac membranes. These data provide no evidence that the peripheral high affinity benzodiazepine binding site is coupled to the cardiac Ca2+ channel. The possibility cannot be excluded that a postulated micromolar affinity benzodiazepine receptor is associated with the Ca2+ channel.
Holck
M
M
Osterrieder
W
W
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism; D009568:Nitrendipine; D011963:Receptors, GABA-A / Q000187:drug effects*
D001570:Benzodiazepinones; D002121:Calcium Channel Blockers; D007473:Ion Channels; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D009568:Nitrendipine; D009543:Nifedipine