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)) was investigated in a study of rabbit ventricular myocytes using the whole-cell patch-clamp technique. Intracellular application of cGMP (100 μM) increased I(Ca), in the absence of isoprenaline or forskolin. 8-Bromo-cGMP (100 μM) and 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP, 400 μM), 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 μM), a phosphodiesterase-resistant cGMP-PK inhibitor. When I(Ca) was increased by bath application of the non-specific phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX, 100 μM), 8-pCPT-cGMP (400 μM) resulted in additional stimulation of I(Ca),. In the presence of 8-pCPT-cGMP, additional applications of isoprenaline (1 μM) or forskolin (1 μM) induced a further increase in I(Ca). From these results, it could be concluded that the activation of cGMP-dependent protein kinase is involved in the facilitation of I(Ca) by cGMP in rabbit ventricular myocytes.