Vascular Smooth Muscle: Structure And Function In Health And Disease by Hai Chi-Ming

Author:Hai, Chi-Ming
Language: eng
Format: epub
ISBN: 9789813144071
Publisher: World Scientific Publishing Company
Published: 2016-10-07T04:00:00+00:00

Fig. 1. Ca2+-induced activation and Ca2+ sensitization of vascular smooth muscle contraction. Vascular smooth muscle contraction is activated principally by an increase in [Ca2+]i due to stimulus-induced entry of extracellular Ca2+ via sarcolemmal Ca2+-permeant ion channels or G protein-coupled receptor (GPCR)-mediated Ca2+ release from the sarcoplasmic reticulum (SR) via inositol 1,4,5-trisphosphate (IP3) receptors. Ca2+ binds to calmodulin (CaM), which activates myosin light chain kinase (MLCK) to phosphorylate serine-19 (pS19) of the two 20-kDa light chain subunits of smooth muscle myosin II. This enables actin interaction, which markedly increases the MgATPase activity of myosin, leading to cross-bridge cycling and contraction driven by the energy derived from the hydrolysis of ATP within the heads of myosin II. Ca2+ sensitization of contraction involves GPCR-mediated activation of the RhoA/Rho-associated kinase (ROCK) pathway leading to inhibition of myosin light chain phosphatase (MLCP), either directly by phosphorylation of the myosin targeting subunit of MLCP (MYPT1) or indirectly via phosphorylation of CPI-17 (the 17-kDa phosphoprotein inhibitor of MLCP). Protein kinase C (PKC) can also induce Ca2+ sensitization via phosphorylation of CPI-17 in some instances. Gq/11: heterotrimeric G proteins coupled to phospholipase Cβ (PLCβ), which hydro-lyses phosphatidylinositol 4,5-bisphosphate (PIP2) to diacylglycerol (DAG) and IP3. G12/13: heterotrimeric G proteins coupled to guanine nucleotide exchange factors for the small GTPase RhoA (Rho-GEFs), which activate RhoA by GDP-GTP exchange. Activated RhoA-GTP activates ROCK.

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