Overview

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.

Full Product Details

Author:   Raouf A. Khalil ,  D. Neil Granger ,  Joey Granger
Publisher:   Morgan & Claypool Publishers
Imprint:   Morgan & Claypool Publishers
Dimensions:   Width: 19.10cm , Height: 0.50cm , Length: 23.50cm
Weight:   0.167kg
ISBN:  

9781615041800

ISBN 10:   161504180
Pages:   62
Publication Date:   01 May 2010
Audience:   College/higher education ,  Professional and scholarly ,  Undergraduate ,  Postgraduate, Research & Scholarly
Format:   Paperback
Publisher's Status:   Active
Availability:   Awaiting stock  
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Table of Contents

Acknowledgments 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

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Brigham and Women's Hospital and Harvard Medical School Boston, Massachusetts

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