Effects of nitroglycerin on ATP-induced Ca(++)-mobilization, Ca(++)-activated K channels and contraction of cultured smooth muscle cells of porcine coronary artery.

Extracellular application of ATP transiently increases the cytosolic-free Ca++ concentration ([Ca++]i) in cultured smooth muscle cells of porcine coronary artery, and this activates large conductance Ca(++)-activated K (Kca) channels. In the present study effects of nitroglycerin (NG) and 4-aminopyridine (4-AP) on [Ca++]; and contraction were studied. 4-AP blocked Kca channels and enhanced the rise of [Ca++]i with oscillation, which led to contraction of the cells. NG activated the Kca channels of 300 picosiemens and inhibited 4-AP-induced contraction and oscillation of [Ca++]i. These results suggest that the vasorelaxant effect of NG involves hyperpolarization of the cell membrane by activating the Kca channels. NG also cause rapid decrease of [Ca++]i during the Ca(++)-mobilization by ATP in Ca-free solution. Similar effects were observed with cyclic GMP, suggesting that the effects of NG on the Kca channels and [Ca++]i were mediated by cyclic GMP.