Regulation of vascular smooth muscle function / Raouf A. Khalil.

Format:

Book

Author/Creator:

Khalil, Raouf A.

Series:

Colloquium series on integrated systems physiology ; #7.

Integrated systems physiology : from molecule to function to disease, 2154-560X ; bk. #7

Language:

English

Subjects (All):

Vascular smooth muscle.

Vascular resistance.

Blood pressure.

Physical Description:

1 online resource (76 p.)

Place of Publication:

[San Rafael, Calif.?] : Morgan & Claypool Life Sciences, 2010.

Language Note:

English

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.

Contents:

1. Introduction

2. Ca2+ Release from the Intracellular Stores

2.1 Inositol Trisphosphate-Induced Ca2+ Release

2.2 Ca2+-Induced Ca2+ Release

3. Ca2+ Entry from the Extracellular Space

3.1 Ca2+ Leak

3.2 Voltage-Gated Ca2+ Channels

3.3 Receptor-Operated (Ligand-Gated) Ca2+ Channels

3.4 Store-Operated Ca2+ Channels

3.5 Stretch-Activated Ca2+ Channels

4. Mechanisms of Ca2+ Homeostasis

4.1 Plasmalemmal Ca2+-ATPase

4.2 The Sodium-Calcium Exchanger

4.3 Sarcoplasmic Reticulum Ca2+-ATPase

4.4 Mitochondria and Ca2+

5. Ca2+-Dependent Myosin Light Chain Phosphorylation

5.1 Intracellular Free Ca2+ Concentration

5.2 Ca2+-Dependent Myosin Light Chain Phosphorylation

5.3 Evidence for Other Mechanisms of Smooth Muscle Contraction

6. Protein Kinase C

6.1 PKC Structure and PKC Isoforms

6.2 PKC Substrates

6.3 Tissue Distribution of PKC

6.4 Subcellular Distribution of PKC

6.5 Mechanisms of PKC Translocation

6.5.1 Conformation-Induced Changes in Hydrophobicity

6.5.2 Lipid Modification

6.5.3 Phosphorylation

6.5.4 Targeting Sequences

6.6 Functions of PKC in VSM

6.7 PKC Activators

6.8 PKC Inhibitors

6.9 Protein Kinase Cascades during VSM Contraction

7. Rho Kinase in Vascular Smooth Muscle

7.1 ROCK Structure and Isoforms

7.2 Tissue Expression of ROCK

7.3 Subcellular Distribution of ROCK

7.4 Regulation of ROCK Activity

7.5 ROCK Substrates

7.6 ROCK and VSM Function

7.7 Rho Kinase Inhibitors

8. Vascular Smooth Muscle Dysfunction and Vascular Disease

9. Summary

References

Author biography.

Notes:

Part of: Colloquium digital library of life sciences.

Series from website.

Title from PDF t.p. (viewed on June 10, 2010).

Includes bibliographical references.

Cited in:

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ISBN:

1-61504-181-8

OCLC:

656436927