The enhancement of catecholamine-induced Cl- current by cyclic GMP revealed using photolabile caged compounds in guinea-pig ventricular cells.

Whole cell currents were recorded in single myocytes dissociated from guinea-pig ventricles, and caged compounds were loaded intracellularly through the patch electrodes. Flash photolysis of caged cyclic GMP (cGMP) increased the amplitudes of both catecholamine-induced Cl- (ICl) and Ca2+ currents (ICa) which were pre-activated by submaximum doses of isoprenaline. Transient activation of ICl by photo-release of cyclic AMP (cAMP) showed a half decay time (t1/2) of 16.7 +/- 1.4 sec (mean +/- S.E.M., n = 14). This decay was markedly delayed by inhibiting phosphodiesterases using 3-isobutyl-1-methyl-xanthine (IBMX). The intracellular application of cGMP (10-50 microM) also prolonged the decay of the ICl response to caged cAMP (t1/2 = 38.0 +/- 7.1 sec, n = 12). These findings strongly support the hypothesis that cGMP facilitates the beta-adrenergic response of ionic currents through the inhibition of phosphodiesterase in mammalian cardiac myocytes.