Modulation of the Ca(2+)-sensitivity in phasic and tonic smooth muscle.
This work describes the relationship between the cytoplasmic free calcium concentration ([Ca2+]i) measured by the fluorescent Ca(2+)-indicator fura-2, the phosphorylation of the myosin light chain and the force development in the phasic longitudinal smooth muscle layer of guinea-pig ileum and the tonic rabbit pulmonary artery. The close temporal relationship between the rise in cytoplasmic Ca2+ and the initiation of force development as well as the rather good correlation between cytoplasmic Ca2+ and force maintenance leaves little doubt about cytoplasmic Ca2+ being the primary regulator of force. However the present experimental evidence indicate that [Ca2+]i and force are not invariably tightly coupled in smooth muscle. A dissociation between the time course of [Ca2+]i and force was found in the tonic rabbit pulmonary artery but not in the phasic ileum of the guinea-pig. In contrast, there was a pronounced decline in the Ca(2+)-sensitivity of the contractile apparatus (desensitization to Ca2+) in the guinea-pig ileum during prolonged depolarization, an observation not found in the pulmonary artery. Such desensitization could reflect the activation of highly active myosin light chain phosphatase(s) and the different Ca(2+)-sensitivities of tonic and phasic smooth muscles can, at least in part, be due to differences in myosin light chain kinase/phosphatase activity ratios. The sensitivity of the regulatory/contractile apparatus to Ca2+ was increased by agonists in intact and in permeabilized preparations. Furthermore a different sensitizing potentiation between different agonists was observed. The mechanism of the "sensitization" of the contractile response to Ca2+ could act through the activation of the phosphorylation of a protein phosphatase inhibitor, thereby inhibiting the myosin light chain phosphatase. The experiments therefore show that different levels of tension may be present at the same [Ca2+]i and indicate that the Ca(2+)-sensitivity can be modulated in smooth muscle.
Himpens
B
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Laboratorium voor Fysiologie, Gasthuisberg O/N, K U Leuven.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D004285:Dogs; D007082:Ileum; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011651:Pulmonary Artery; D012433:Ryanodine / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D012433:Ryanodine; D010656:Phenylephrine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002217:Carbachol; D009219:Myosin-Light-Chain Kinase; D011188:Potassium; D002118:Calcium