Myosin phosphorylation and Ca2+ sensitization in porcine coronary arterial smooth muscle stimulated with endothelin-1.
We examined the mechanism of endothelin-1-induced contraction in the porcine coronary artery by assessing the changes in myosin light chain phosphorylation and cytosolic Ca2+ concentration ([Ca2+]i) determined by fura-2 and front-surface fluorometry. Endothelin-1 induced a rapid phosphorylation of myosin both in the presence and in the absence of extracellular Ca2+. During the later phase of contraction (5-30 min), the tension and [Ca2+]i were maintained, while the phosphorylated myosin decreased in the presence of extracellular Ca2+. At a similar extent of [Ca2+]i elevation, endothelin-1 induced a greater tension development than did 118 mM K(+)-depolarization and this was not attributed to a greater degree of phosphorylation of myosin. In the Ca(2+)-depleted strips, endothelin-1 induced a slow and transient contraction without an increase in either [Ca2+]i or myosin phosphorylation. Therefore, in addition to the activation of mechanisms of [Ca2+]i-myosin phosphorylation, endothelin-1 may activate additional calcium regulatory mechanisms which may thus increase the Ca2+ sensitivity of contractile elements while also enhance and prolong the contractions in the porcine coronary artery.
Kodama
M
M
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yamamoto
H
H
Kanaide
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D016232:Endothelins / Q000494:pharmacology*; D016257:Fura-2 / Q000737:chemistry; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009218:Myosins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013552:Swine
D016232:Endothelins; D009218:Myosins; D002118:Calcium; D016257:Fura-2