Abstract
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 (10-5M), 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 (5×10-6 to 5×10-5M) but not by diphenhydramine. Also, the amplitude of DAD decreased after verapamil (10-7 to 3×10-6M) and lidocaine (4×10-5 to 8×10-5M). To investigate indirect evidence of increased cyclic AMP mediation in this histamine induced DAD, we studied the effects of a phosphodiesterase inhibitor (papaverine 10-5M) or activator (N-methylimidazole 20mM) 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.
