[Cellular mechanisms of smooth muscle contraction].
Myosin is an ATPase, able to form filaments with actin, thus initiating smooth muscle contraction (conversion of chemical energy into mechanical energy). Myosin activity is regulated by cytosolic calcium, via a calcium-calmodulin-MLCK-dependent phosphorylation. Extrusion of cytosolic calcium via calcium pumps (in the plasma membrane and sarcoplasmic reticulum) and via a sodium-calcium exchange allow smooth muscle cells to maintain their resting state. Constrictor agonists (hormones, neurotransmitters or drugs) act at membrane receptors inducing: (i) a fast and transient calcium mobilization from the sarcoplasmic reticulum, via phospholipase C (PLC) stimulation and inositol triphosphate (IP3) production or via a "calcium-induced calcium release" mechanism and opening of calcium channels in the sarcoplasmic reticulum and (ii) a slow and maintained mobilization of extracellular calcium, via the opening of voltage-dependent calcium channels in plasma membranes. Smooth muscle relaxation is ensured by a phosphatase which hydrolyzes phosphorylated myosin and decreases the calcium sensitivity of the contractile apparatus. Calcium signal is regulated at that level by: (i) protein kinase C, tyrosine kinase and arachidonic acid which inhibit phosphatase activity and (ii) cyclic AMP (cAMP) and cyclic GMP (cGMP) which enhance phosphatase activity. A second regulatory site is situated at the level of the non-contractile calcium compartment, which buffers signal transduction and where cGMP and/or cAMP enhance calcium extrusion mechanisms.
INSERM U400, Faculté de Médecine, Créteil. garay@im3.inserm.fr
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D020013:Calcium Signaling; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology* / Q000201:enzymology / Q000502:physiology*
D009124:Muscle Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000252:Calcium-Transporting ATPases