The physiology, pathophysiology and therapeutic potential of gap junctions in smooth muscle

G. Lagaud, Kelvin Davies, K. Venkateswarlu, G. J. Christ

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Phenotypic variability in smooth muscle cells accounts, in large part, for the incredible functional diversity required of the involuntary hollow organs of the body (i.e., respiratory passages, blood vessels, gastrointestinal tract, urogenital tract, etc.). In all instances coordination of smooth muscle cell responses, that is, contraction and relaxation, is critical to normal organ function. While numerous biological mechanisms exist for coordinating smooth muscle cell responses, intercellular communication through gap junctions represents a common denominator present in all organ systems. In this report, we review the evidence documenting the presence and functional significance of myocyte gap junctions to physiologically distinct organ systems, and furthermore, provide some examples of their putative roles in organ pathology. Finally, we advance the thesis that despite their ubiquity and heterogeneous expression, gap junctions are nonetheless potentially attractive therapeutic targets for the treatment of certain smooth muscle disorders. Their therapeutic efficacy will necessarily hinge on the existence of connexin isoform-selective junctional effects. The overall rationale for targeting the intercellular pathway is therefore analogous to strategies that target other ubiquitously expressed ion channels, such as calcium or potassium channels. Such strategies have proved efficacious for the treatment of a wide range of human smooth muscle disorders including hypertension, urinary incontinence and sexual function.

Original languageEnglish (US)
Pages (from-to)427-440
Number of pages14
JournalCurrent Drug Targets
Volume3
Issue number6
DOIs
StatePublished - Dec 2002

Fingerprint

Gap Junctions
Physiology
Smooth Muscle Myocytes
Smooth Muscle
Muscle
Muscular Diseases
Cells
Connexins
Potassium Channels
Urinary Incontinence
Calcium Channels
Ion Channels
Muscle Cells
Blood Vessels
Gastrointestinal Tract
Protein Isoforms
Therapeutics
Pathology
Hypertension
Blood vessels

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

Cite this

The physiology, pathophysiology and therapeutic potential of gap junctions in smooth muscle. / Lagaud, G.; Davies, Kelvin; Venkateswarlu, K.; Christ, G. J.

In: Current Drug Targets, Vol. 3, No. 6, 12.2002, p. 427-440.

Research output: Contribution to journalArticle

Lagaud, G. ; Davies, Kelvin ; Venkateswarlu, K. ; Christ, G. J. / The physiology, pathophysiology and therapeutic potential of gap junctions in smooth muscle. In: Current Drug Targets. 2002 ; Vol. 3, No. 6. pp. 427-440.
@article{36138e142ff94f85b3cb4ceec2f2363f,
title = "The physiology, pathophysiology and therapeutic potential of gap junctions in smooth muscle",
abstract = "Phenotypic variability in smooth muscle cells accounts, in large part, for the incredible functional diversity required of the involuntary hollow organs of the body (i.e., respiratory passages, blood vessels, gastrointestinal tract, urogenital tract, etc.). In all instances coordination of smooth muscle cell responses, that is, contraction and relaxation, is critical to normal organ function. While numerous biological mechanisms exist for coordinating smooth muscle cell responses, intercellular communication through gap junctions represents a common denominator present in all organ systems. In this report, we review the evidence documenting the presence and functional significance of myocyte gap junctions to physiologically distinct organ systems, and furthermore, provide some examples of their putative roles in organ pathology. Finally, we advance the thesis that despite their ubiquity and heterogeneous expression, gap junctions are nonetheless potentially attractive therapeutic targets for the treatment of certain smooth muscle disorders. Their therapeutic efficacy will necessarily hinge on the existence of connexin isoform-selective junctional effects. The overall rationale for targeting the intercellular pathway is therefore analogous to strategies that target other ubiquitously expressed ion channels, such as calcium or potassium channels. Such strategies have proved efficacious for the treatment of a wide range of human smooth muscle disorders including hypertension, urinary incontinence and sexual function.",
author = "G. Lagaud and Kelvin Davies and K. Venkateswarlu and Christ, {G. J.}",
year = "2002",
month = "12",
doi = "10.2174/1389450023347399",
language = "English (US)",
volume = "3",
pages = "427--440",
journal = "Current Drug Targets",
issn = "1389-4501",
publisher = "Bentham Science Publishers B.V.",
number = "6",

}

TY - JOUR

T1 - The physiology, pathophysiology and therapeutic potential of gap junctions in smooth muscle

AU - Lagaud, G.

AU - Davies, Kelvin

AU - Venkateswarlu, K.

AU - Christ, G. J.

PY - 2002/12

Y1 - 2002/12

N2 - Phenotypic variability in smooth muscle cells accounts, in large part, for the incredible functional diversity required of the involuntary hollow organs of the body (i.e., respiratory passages, blood vessels, gastrointestinal tract, urogenital tract, etc.). In all instances coordination of smooth muscle cell responses, that is, contraction and relaxation, is critical to normal organ function. While numerous biological mechanisms exist for coordinating smooth muscle cell responses, intercellular communication through gap junctions represents a common denominator present in all organ systems. In this report, we review the evidence documenting the presence and functional significance of myocyte gap junctions to physiologically distinct organ systems, and furthermore, provide some examples of their putative roles in organ pathology. Finally, we advance the thesis that despite their ubiquity and heterogeneous expression, gap junctions are nonetheless potentially attractive therapeutic targets for the treatment of certain smooth muscle disorders. Their therapeutic efficacy will necessarily hinge on the existence of connexin isoform-selective junctional effects. The overall rationale for targeting the intercellular pathway is therefore analogous to strategies that target other ubiquitously expressed ion channels, such as calcium or potassium channels. Such strategies have proved efficacious for the treatment of a wide range of human smooth muscle disorders including hypertension, urinary incontinence and sexual function.

AB - Phenotypic variability in smooth muscle cells accounts, in large part, for the incredible functional diversity required of the involuntary hollow organs of the body (i.e., respiratory passages, blood vessels, gastrointestinal tract, urogenital tract, etc.). In all instances coordination of smooth muscle cell responses, that is, contraction and relaxation, is critical to normal organ function. While numerous biological mechanisms exist for coordinating smooth muscle cell responses, intercellular communication through gap junctions represents a common denominator present in all organ systems. In this report, we review the evidence documenting the presence and functional significance of myocyte gap junctions to physiologically distinct organ systems, and furthermore, provide some examples of their putative roles in organ pathology. Finally, we advance the thesis that despite their ubiquity and heterogeneous expression, gap junctions are nonetheless potentially attractive therapeutic targets for the treatment of certain smooth muscle disorders. Their therapeutic efficacy will necessarily hinge on the existence of connexin isoform-selective junctional effects. The overall rationale for targeting the intercellular pathway is therefore analogous to strategies that target other ubiquitously expressed ion channels, such as calcium or potassium channels. Such strategies have proved efficacious for the treatment of a wide range of human smooth muscle disorders including hypertension, urinary incontinence and sexual function.

UR - http://www.scopus.com/inward/record.url?scp=0036888948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036888948&partnerID=8YFLogxK

U2 - 10.2174/1389450023347399

DO - 10.2174/1389450023347399

M3 - Article

C2 - 12448695

AN - SCOPUS:0036888948

VL - 3

SP - 427

EP - 440

JO - Current Drug Targets

JF - Current Drug Targets

SN - 1389-4501

IS - 6

ER -