In rat mesenteric artery cells, L-type Ca2+ channel currents are enhanced by intracellular cAMP and suppressed by cGMP, providing a mechanistic basis for the vasodilating action of drugs like nitroglycerin.
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 μM) but enhanced by Bay K 8644 (5 μM), which suggests that the inward currents are carried almost exclusively by L-type Ca2+ channels. Application of dibutyryl cAMP (0.1–1 μM) and forskolin (0.01–1 μM) 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 μM). Application of 8-bromo-cGMP (0.01–1 μM) and the cGMP inducer nitroglycerin (0.01–1 μM) 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 μM). 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.
No takes yet. Share an insight, caveat, or question.
Taguchi et al. (1997) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: