Effects of cAMP and cGMP on L-type calcium channel currents in rat mesenteric artery cells.

L-type Ca2+ channel currents in cultured rat mesenteric artery smooth muscle cells were recorded by the cell-attached patch-clamp technique. Depolarizing voltage steps from a holding potential of -40 mV elicited voltage-dependent inward Ba2+ currents. The inward currents were inhibited by nifedipine (10 microM) but enhanced by Bay K 8644 (5 microM), which suggests that the inward currents are carried almost exclusively by L-type Ca2+ channels. Application of dibutyryl cAMP (0.1-1 microM) and forskolin (0.01-1 microM) enhanced the activity of these Ca2+ channels. The dibutyryl cAMP induced enhancement of Ca2+ channels was antagonized by the serine/threonine kinase inhibitor H-8 (1 microM). Application of 8-bromo-cGMP (0.01-1 microM) and the cGMP inducer nitroglycerin (0.01-1 microM) inhibited the activity of these Ca2+ channels, and the inhibition of channel activity induced by 8-bromo-cGMP was antagonized by the serine/threonine kinase inhibitor H-8 (1 microM). These results suggest that in rat mesenteric artery cells, the L-type Ca2+ channel current is enhanced by a rise in intracellular cAMP levels and suppressed by a rise in intracellular cGMP levels. Furthermore, cGMP-induced Ca2+ channel inhibition may play a role in the expression of the nitric oxide-mediated vasodilating action of drugs such as nitroglycerin and atrial natriuretic peptide.