The potent vasodilator action of cyclic GMP-dependent protein kinase (cGK) involves decreasing the Ca

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Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with regulation of the L-type Ca2+-channel current (Ice) through the opposite actions of two second messengers, cyclic AMP and cyclic GMP.While cyclic AMP stimulation of 1c. is mediated by the activation of cyclic AMP-dependent protein kinase, inhibition of 'Ca by cyclic GMP in frog heart is largely mediated by activation of cyclic AMP phosphodiesterase. The present patch-clamp study reveals that, in rat ventricular cells, cyclic GMP can also regulate ICa via activation of endogenous cyclic GMP-dependent protein kinase (cGMP-PK). Indeed, the effect of cyclic GMP on 1Ca was mimicked by intracellular perfusion with the proteolytic active fragment of purified cGMP-PK.Moreover, cGMP-PK immunoreactivity was detected in pure rat ventricular myocytes by using a specific polyclonal antibody. These results demonstrate a dual mechanism for the inhibitory action of cyclic GMP in heart, as well as a physiological role for cGMP-PK in the control of mammalian heart function.