The intracellular calcium-force relationship in vascular smooth muscle. Time- and stimulus-dependent dissociation.

An increase in cytosolic Ca2+ level [( Ca2+]cyt) initiates smooth muscle contraction. Simultaneous measurements of [Ca2+]cyt and muscle tension provide insight into the Ca2+ regulation of smooth muscle. The photoprotein aequorin and the fluorescent Ca2+ indicator fura-2 have been used for this purpose. Although there are some differences between aequorin signal and fura-2 signal, comparison between [Ca2+]cyt and muscle tension in vascular smooth muscle indicates that high K+ and agonists that operate via specific receptors (receptor-agonists) induce sustained contraction whereas stimulated [Ca2+]cyt gradually decreases during prolonged exposure to agonists. Furthermore, greater contraction is produced by receptor-agonists than high K+ at a given [Ca2+]cyt. By contrast, cyclic AMP and cyclic GMP decrease muscle tension more strongly than [Ca2+]cyt. These results suggest that contractility of vascular smooth muscle is regulated not only by [Ca2+]cyt, but also by other mechanisms, possibly including Ca2+ sensitivity of the contractile elements. Ca2+ sensitization may be due to activation of protein kinase C.