cGMP facilitates calcium current via cGMP-dependent protein kinase in isolated rabbit ventricular myocytes

The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on L-type Ca current (I-Ca) as investigated in a study of rabbit ventricular myocytes using the whole-cell patch-clamp technique, Intracellular application of cGMP (100 mu M) increased I-Ca in the absence of isoprenaline or forskolin. 8-Bromo-cGMP (100 mu M) and 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP, 400 mu M), relatively specific stimulators of cGMP-dependent protein kinase (cGMP-PK). also increased I-Ca. The stimulatory effect of 8-pCPT-cGMP was suppressed by Rp-8-chlorophenylthio-cGMP (400 mu M), a phosphodiesterase-resistant cGMP-PK inhibitor. When I-Ca was increased bq bath application of the non-specific phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX. 100 mu M). 8-pCPT-cGMP (400 mu M) resulted in additional stimulation of I-Ca. In the presence of 8-pCPT-cGMP. additional applications of isoprenaline (1 mu M) or forskolin (1 mu M) induced a further increase in I-Ca. From these results, it could be concluded that the activation of cGMP-defendent protein kinase is involved in the facilitation of I-Ca by cGMP in rabbit ventricular myocytes.