Alteration of the [Ca 2+ ] i ‐force relationship during the vasorelaxation induced by a Ca 2+ channel blocker SR33805 in the porcine coronary artery

The mechanism of vasorelaxation induced by SR33805 was investigated by simultaneously monitoring the cytosolic Ca 2+ concentration ([Ca 2+ ] i ) and force, and by determining level of myosin light chain (MLC) phosphorylation in the medial strip of the porcine coronary artery. SR33805 inhibited the sustained increases in [Ca 2+ ] i and force (IC 50 ; 3.2±1.0 and 49.4±27.5 n M , respectively) induced by 118 m M K + ‐depolarization. There was about a 10 fold difference in the inhibitory potency between [Ca 2+ ] i and force. SR33805 completely inhibited the [Ca 2+ ] i elevation induced by a thromboxane A 2 analogue, U46619 and histamine, at concentrations (1 μ M ) higher than those required for the complete inhibition of K + ‐depolarization induced [Ca 2+ ] i elevation. SR33805 had no effect on the [Ca 2+ ] i elevation induced by histamine or caffeine in the absence of extracellular Ca 2+ . SR33805 caused a leftward shift of the [Ca 2+ ] i ‐force relationship of the contraction induced by cumulative application of extracellular Ca 2+ during 118 m M K + ‐depolarization. The relationship between [Ca 2+ ] i and MLC phosphorylation also shifted to the left by SR33805, while the relationship between MLC phosphorylation and force remained unaffected. In conclusion, SR33805 caused an apparent leftward shift of the [Ca 2+ ] i ‐force relationship, accompanied by a greater degree of MLC phosphorylation for a given level of [Ca 2+ ] i . The mechanism of this leftward shift, however, still remains to be elucidated.British Journal of Pharmacology (2000) 131 , 1597–1606; doi: 10.1038/sj.bjp.0703721