[Calcium regulation of smooth muscle contractility].
Simultaneous measurements of cytoplasmic Ca2+ level [( Ca2+]i) and muscle contraction in smooth muscle indicated that [Ca2+]i gradually decreases during sustained contraction. This time-dependent dissociation has been explained by the latch bridge hypothesis, positive cooperativity between phosphorylated and non-phosphorylated crossbridges, involvement of cytoskeleton phosphorylation, or connection between myosin and actin filaments by caldesmon. Furthermore, it has been found that receptor agonists induce greater contraction than high K+ for a given increase in [Ca2+]i. This stimulus-dependent dissociation may be due to the receptor agonists-induced activation of protein kinase C which in turn decreases the inhibitory effect of calponin on the actin-myosin interaction, resulting in an apparent Ca2+ sensitization. Thus, the contractions induced by receptor agonists are due not only to the increase in [Ca2+]i but also to the increase in Ca2+ sensitivity of contractile elements. Ca2+ channel blockers inhibit the increase in [Ca2+]i but not the Ca2+ sensitization, and this may be the reason why these blockers are relatively weak inhibitors of the contraction induced by receptor agonists. By contrast, cyclic AMP and cyclic GMP decrease the Ca2+ sensitivity of contractile elements in addition to their effects to decrease [Ca2+]i.
Karaki
H
H
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D013995:Time
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000242:Cyclic AMP; D009218:Myosins; D006152:Cyclic GMP; D002118:Calcium