Differential regulation of MLC20 phosphorylation in tonic and phasic smooth muscles of the stomach
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xvi DIFFERENTIAL REGULATION OF MLC20 PHOSPHORYLATION IN TONIC AND PHASIC SMOOTH MUSCLES OF THE STOMACH By Othman A. Al-Shboul, Ph.D. A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2011 Major Director: S.Murthy Karnam Professor, Department of Physiology Gastrointestinal (GI) smooth muscle possesses distinct regional and functional properties that distinguish it from other types of visceral and vascular smooth muscle. On the basis of electrical properties and contractile phenotype, GI smooth muscles have been classified into phasic (non-sphinteric) and tonic (sphinteric) smooth muscles. The biochemical basis of phasic and tonic phenotypes of smooth muscle is not clear and is the major question of inquiry of the present study. Phosphorylation of Ser 19 on the 20 kDa myosin light chain (MLC) is essential for acto-myosin interaction and contraction in both phasic and tonic muscles. The levels of MLC20
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Ca2+/calmodulin/MLCK pathway initiates, and RhoA/ROCK maintains, the internal anal sphincter smooth muscle tone.
IT IS WELL KNOWN that smooth muscle contraction, whether spontaneous or following pharmacological stimulation, occurs in two phases: the initial phasic followed by the tonic phase (1, 2, 5, 6, 11, 12, 14, 16, 17, 22, 23, 25, 33, 37). Initial phasic contraction is critically dependent on an increase in the intracellular levels of Ca often caused by G protein-coupled receptor (GPCR) activation. T...
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