Ca2+ -induced Ca2+ desensitization of myosin light chain phosphorylation and contraction in phasic smooth muscle.
The temporal relationship between Ca2+ -induced contraction and phosphorylation of 20 kDa myosin light chain (MLC) during a step increase in Ca2+ was investigated using permeabilized phasic smooth muscle from rabbit portal vein and guinea-pig ileum at 25 degrees C. We describe here a Ca2+ -induced Ca2+ desensitization phenomenon in which a transient rise in MLC phosphorylation is followed by a transient rise in contractile force. During and after the peak contraction, the force to phosphorylation ratio remained constant. Further treatment with cytochalasin D, an actin fragmenting agent, did not affect the transient increase in phosphorylation, but blocked force development. Together, these results indicate that the transient phosphorylation causes the transient contraction and that neither inhomogeneous contractility nor reduced thin filament integrity effects the transient phosphorylation. Lastly, we show that known inhibitors to MLC kinase kinases and to a Ca2+ -dependent protein phosphatase did not eliminate the desensitized contractile force. This study suggests that the Ca2+ -induced Ca2+ desensitization phenomenon in phasic smooth muscle does not result from any of the known intrinsic mechanisms involved with other aspects of smooth muscle contractility.
Murahashi
T
T
Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, DC 20007, USA.
Fujita
A
A
Kitazawa
T
T
D000818:Animals; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D004789:Enzyme Activation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism* / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits
D065095:Calcineurin Inhibitors; D018994:Myosin Light Chains; D015638:Cytochalasin D; D009219:Myosin-Light-Chain Kinase; D010749:Phosphoprotein Phosphatases; D043263:Myosin-Light-Chain Phosphatase; D002118:Calcium