Histamine induced or enhanced delayed afterdepolarization and triggered activity in guinea-pig papillary muscles. A preliminary study.
We used standard microelectrode techniques to study the histamine induced or enhanced delayed afterdepolarization (DAD) and triggered activity (TA) of guinea-pig papillary muscle superfused with low-potassium Tyrode's solution. Before histamine, a series of driven action potentials did not induce DAD and TA. Immediately after histamine (10(-5)M), DAD was induced and, finally, TA was induced after high rate pacing (150/min to 300/min). The effect of histamine was antagonized by cimetidine (5 X 10(-6) to 5 X 10(-5)M) but not by diphenhydramine. Also, the amplitude of DAD decreased after verapamil (10(-7) to 3 X 10(-6)M) and lidocaine (4 X 10(-5) to 8 X 10(-5)M). To investigate indirect evidence of increased cyclic AMP mediation in this histamine induced DAD, we studied the effects of a phosphodiesterase inhibitor (papaverine 10(-5)M) or activator (N-methylimidazole 20 mM) on the histamine induced or enhanced DAD. The former enhanced and the latter depressed the histamine-induced (or enhanced) DAD. Thus, histamine may induce or enhance the DAD and TA by increasing the slow inward current. This mechanism may be mediated by histamine H2-receptors and the adenylate cyclase system in the cardiac ventricular muscle.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004155:Diphenhydramine / Q000494:pharmacology; D004594:Electrophysiology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008839:Microelectrodes; D010208:Papaverine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology
D006633:Histamine Antagonists; D007093:Imidazoles; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine; D010208:Papaverine; D000242:Cyclic AMP; C018100:1-methylimidazole