Cyclic GMP regulates the Ca-channel current in guinea pig ventricular myocytes

The effect of intracellular perfusion with cyclic GMP (cGMP) on Ca current (Ica) was investigated in Cs-loaded isolated cells from guinea pig ventricle using the whole-cell patch-clamp technique and a perfused patch pipette. cGMP (5 microM) strongly reduced Ica which had been elevated by intracellular perfusion with 50 microM of either cyclic AMP (cAMP) or its hydrolysis-resistant analog 8-Bromo-cAMP. In addition, cGMP prevented the stimulation of Ica by IBMX, a phosphodiesterase inhibitor. The membrane permeant cGMP analog 8-Bromo-cGMP (100 microM), when applied outside the cell, also antagonized the stimulatory effect of IBMX on Ica. It is concluded that cGMP inhibits Ica in guinea pig ventricular cells by a mechanism different from the activation of a cGMP-stimulated phosphodiesterase recently found in frog ventricular cells.