Jj. Janvier et al., Diazepam reduces action potential duration in guinea-pig papillary muscle by a cAMP-dependent mechanism, LIFE SCI, 64(25), 1999, pp. 2383-2389
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.