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.
Karaki
H
H
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism
D000242:Cyclic AMP; D011493:Protein Kinase C; D009218:Myosins; D006152:Cyclic GMP; D002118:Calcium