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.
Fujino
K
K
Second Department of Internal Medicine, School of Medicine, Tokushima University, Japan.
Nakaya
S
S
Wakatsuki
T
T
Miyoshi
Y
Y
Nakaya
Y
Y
Mori
H
H
Inoue
I
I
D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006152:Cyclic GMP / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D013552:Swine
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D005996:Nitroglycerin; D006152:Cyclic GMP; D002118:Calcium