Diazepam reduces action potential duration in guinea-pig papillary muscle by a cAMP-dependent mechanism

In this study, we have analyzed the role of cyclic AMP (cAMP) as the mediat or of the decrease in action potential duration induced by diazepam. Diazep am (1-100 mu M) reduced, in a dose-dependent manner, the duration of intrac ellular action potential recorded in the papillary muscle obtained from the right ventricle of the guinea pig heart. This effect was mimicked by the a nalog of cyclic AMP, 8-Br-cAMP (100 mu M), but not by gamma-amino-butyric a cid (GABA). Also, the selective antagonist of the benzodiazepine receptors, flumazenil did not modify the effect of diazepam. The diazepam-induced sho rtening of action potential duration was partially antagonized by the inhib itor of cAMP synthesis carbachol (1 mu M) or the blocker of the cAMP-depend ent protein kinase A, Rp-cAMP[S] (1 mu M). These results indicate that cycl ic AMP is involved in the diazepam-induced shortening of the action potenti al duration of the guinea pig papillary muscle.