Alteration of the [Ca2+](i)-force relationship during the vasorelaxation induced by a Ca2+ channel blocker SR33805 in the porcine coronary artery

1 The mechanism of vasorelaxation induced by SR33805 was investigated by si multaneously monitoring the cytosolic Ca2+ concentration ([Ca2+](i)) and fo rce, and by determining level of myosin light chain (MLC) phosphorylation i n the medial strip of the porcine coronary artery. 2 SR33805 inhibited the sustained increases in [Ca2+](i) and force (IC50; 3 .2 +/- 1.0 and 49.4 +/- 27.5 nM, respectively) induced by 118 mM K+-depolar ization. There was about a 10 fold difference in the inhibitory potency bet ween [Ca2+](i) and force. 3 SR33805 completely inhibited the [Ca2+](i) elevation induced by a thrombo xane A(2) analogue, U46619 and histamine, at concentrations (1 muM) higher than those required for the complete inhibition of K+-depolarization induce d [Ca2+](i) elevation. 4 SR33805 had no effect on the [Ca2+](i) elevation induced by histamine or caffeine in the absence of extracellular Ca25 SR33805 caused a leftward shift of the [Ca2+](i)-force relationship of th e contraction induced by cumulative application of extracellular Ca2+ durin g 118 mM K+-depolarization. The relationship between [Ca2+](i) and MLC phos phorylation also shifted to the left by SR33805, while the relationship bet ween MLC phosphorylation and force remained unaffected. 6 In conclusion, SR33805 caused an apparent leftward shift of the [Ca2+](i) -force relationship, accompanied by a greater degree of MLC phosphorylation for a given level of [Ca2+](i). The mechanism of this leftward shift, howe ver, still remains to be elucidated.