Inotropic agents modulate gap junctional conductance between cardiac myocytes.
Cardiac gap junction channels mediate the intercellular exchange of second messenger and small molecules. Through effects on conduction velocity, enhanced junctional conductance (gj) facilitates rapid and synchronous activation of the contractile myocardium, whereas reduced gj slows activation and could contribute to arrhythmogenesis. We report here that gj is enhanced by agents that elevate intracellular adenosine 3',5'-cyclic monophosphate (cAMP; 8-bromo-cAMP or isoproterenol) and is depressed by agents that elevate intracellular guanosine 3',5'-cyclic monophosphate (cGMP; 8-bromo-cGMP or carbachol). Both effects occur with a time course comparable to the inotropic events mediated by these agents. The effect of cAMP on gj is not dependent on simultaneous changes in intracellular calcium; however, during calcium-overload conditions cAMP can precipitate calcium-dependent uncoupling. These results indicate that cyclic nucleotide-dependent changes in gj may contribute to the inotropic effects of these agents. Furthermore, the results suggest that the inotropic effect of cAMP includes a calcium-independent component.
Burt
J M
JM
Department of Physiology, University of Arizona, Tucson 85724.
Spray
D C
DC
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D004553:Electric Conductivity; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007365:Intercellular Junctions / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D051381:Rats
D002316:Cardiotonic Agents; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002110:Caffeine; D002217:Carbachol; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium