Effects of cAMP and cGMP on L-Type Calcium Channel Currents in Rat Mesenteric Artery Cells

[摘要] References(27)Cited-By(13)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-bromocGMP (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.

[学科分类] 药理学

[关键词] Ca2+ channel;cAMP;cGMP;Mesenteric artery;Patch-clamp