Tuning smooth muscle contraction by molecular motors.
As in striated muscle, smooth muscle cells (SMC) contract by Ca2+ activated cyclic interaction between actin and type II myosin. However, smooth muscle maintains tone at basal activating Ca2+ and low energetic cost during sustained activation. This review analyzes the regulation of phasic and tonic contraction of SMC on the molecular level. Type II myosin is the molecular motor also of smooth muscle contraction. Six myosin heavy chain (MHC) isoenzymes (four smooth muscle, two nonmuscle) and five myosin light chain (MLC) isoforms (two 17 kDa, two 20 kDa, one 23 kDa) are expressed in SMC. These myosin subunits could be generated by alternative splicing or by differential gene expression. Thus different myosin isoenzymes are generated which may be modified posttranslationally by phosphorylation, affecting the contractile state of the SMC. Furthermore, they may be part of distinct contractile systems which are targeted by different second messenger cascades and are recruited differentially during activation, electromechanical, and pharmacomechanical coupling. Low energy consumption, shortening velocity, and MLC20 phosphorylation at low Ca2+ activation levels during tone maintenance ("latch") could be explained by a switch from smooth muscle myosin to nonmuscle myosin activation upon prolonged activation.
Morano
Ingo
I
Max Delbrück Centrum for Molecular Medicine and Humboldt University, Johannes Müller Institute for Physiology, Berlin, Germany. Imorano@mdc-berlin.de
D017398:Alternative Splicing; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D020409:Molecular Motor Proteins / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000737:chemistry / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism
D007527:Isoenzymes; D020409:Molecular Motor Proteins; D018994:Myosin Light Chains; D009219:Myosin-Light-Chain Kinase; D018995:Myosin Heavy Chains