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

摘要

class="enumerated" style="list-style-type:decimal">The mechanism of vasorelaxation induced by SR33805 was investigated by simultaneously monitoring the cytosolic Ca²⁺ concentration ([Ca²⁺]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 [Ca²⁺]i and force (IC50; 3.2±1.0 and 49.4±27.5 nM, respectively) induced by 118 mM K⁺-depolarization. There was about a 10 fold difference in the inhibitory potency between [Ca²⁺]i and force.SR33805 completely inhibited the [Ca²⁺]i elevation induced by a thromboxane A2 analogue, U46619 and histamine, at concentrations (1 μM) higher than those required for the complete inhibition of K⁺-depolarization induced [Ca²⁺]i elevation.SR33805 had no effect on the [Ca²⁺]i elevation induced by histamine or caffeine in the absence of extracellular Ca²⁺.SR33805 caused a leftward shift of the [Ca²⁺]i-force relationship of the contraction induced by cumulative application of extracellular Ca²⁺ during 118 mM K⁺-depolarization. The relationship between [Ca²⁺]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 [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, however, still remains to be elucidated.