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E-book
Author Khalil, Raouf A.

Title Regulation of vascular smooth muscle function / Raouf A. Khalil
Published [San Rafael, CA] : Morgan & Claypool Life Sciences, [2010]
©2010
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Colloquium Digital Library of Life Sciences    View Resource Record  

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Description 1 online resource
Series Integrated systems physiology, 2154-5626 ; #7
Colloquium series on integrated systems physiology ; #7. 2154-5626
Contents Introduction -- Ca2+ Release from the Intracellular Stores -- Ca2+ Entry from the Extracellular Space -- Mechanisms of Ca2+ Homeostasis -- Ca2+-Dependent Myosin Light Chain Phosphorylation -- Protein Kinase C -- Rho Kinase in Vascular Smooth Muscle -- Vascular Smooth Muscle Dysfunction and Vascular Disease -- Summary -- References -- Author Biography
Summary Vascular smooth muscle (VSM) constitutes most of the tunica media in blood vessels and plays an important role in the control of vascular tone. Ca2+ is a major regulator of VSM contraction and is strictly regulated by an intricate system of Ca2+ mobilization and Ca2+ homeostatic mechanisms. The interaction of a physiological agonist with its plasma membrane receptor stimulates the hydrolysis of membrane phospholipids and increases the generation of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 stimulates Ca2+ release from the intracellular stores in the sarcoplasmic reticulum. Agonists also stimulate Ca2+ influx from the extracellular space via voltage-gated, receptor-operated, and store-operated channels. Ca2+ homeostatic mechanisms tend to decrease the intracellular free Ca2+ concentration ([Ca2+]i) by activating Ca2+ extrusion via the plasmalemmal Ca2+ pump and the Na+/Ca2+ exchanger and the uptake of excess Ca2+ by the sarcoplasmic reticulum and possibly the mitochondria. A threshold increase in [Ca2+]i activates Ca2+-dependent myosin light chain (MLC) phosphorylation, stimulates actin-myosin interaction, and initiates VSM contraction. The agonist-induced maintained increase in DAG also activates specific protein kinase C (PKC) isoforms, which in turn cause phosphorylation of cytoplasmic substrates that increase the contractile myofilaments force sensitivity to Ca2+ and thereby enhance VSM contraction. Agonists could also activate Rho kinase (ROCK), leading to inhibition of MLC phosphatase and further enhancement of the myofilaments force sensitivity to Ca2+. The combined increases in [Ca2+]i, PKC and ROCK activity cause significant vasoconstriction and could also stimulate VSM hypertrophy and hyperplasia. The protracted and progressive activation of these processes could lead to pathological vascular remodeling and vascular disease
Analysis Signal transduction
Vascular smooth muscle
Calcium
Blood pressure
AngII, angiotensin II
ATP, adenosine triphosphate
CPI-17, PKC-potentiated phosphatase inhibitor protein-17 kDa
CAM, calmodulin
DAG, diacylglycerol
ET-1, endothelin
IP3, inositol 1,4,5-trisphosphate
MAPK, mitogen-activated protein kinase
MARCKs, myristoylated alanine-rich C-kinase substrate
MEK, MAPK kinase
MLC, myosin light chain
NCX, Na+-Ca2+ exchanger
PDBu, phorbol 12,13-dibutyrate; PIP2, phosphatidylinositol 4,5-bisphosphate
PKC, protein kinase C
PMA, phorbol myristate acetate
RACKs, receptors for activated C-kinase
ROCK, Rho-kinase
VSMC, vascular smooth muscle cell
Main Series Colloquium series on integrated systems physiologyfrom molecule to function to disease
Notes Title from PDF t.p. (viewed Aug. 17, 2011)
Bibliography Includes bibliographical references
Notes English
Subject Muscle contraction.
Muscle, Smooth, Vascular -- physiology.
Calcium Channels.
Myosins -- physiology.
Vascular Diseases -- etiology.
Vasoconstriction -- physiology.
Vascular smooth muscle.
Vascular resistance.
Blood pressure.
Form Electronic book
Author National Library of Medicine (U.S.)
ISBN 9781615041817
Other Titles Colloquium digital library of life sciences: Collection 1
NCBI Bookshelf