Caveolae and sarcoplasmic reticular coupling in smooth muscle cells of pressurised arteries: the relevance for Ca2+ oscillations and tone

Linda Shaw; Michele A Sweeney; Stephen C O'Neill; Carolyn J P Jones; Clare Austin; Michael J Taggart

doi:10.1016/j.cardiores.2005.12.016

Caveolae and sarcoplasmic reticular coupling in smooth muscle cells of pressurised arteries: the relevance for Ca2+ oscillations and tone

Linda Shaw, Michele A Sweeney, Stephen C O'Neill, Carolyn J P Jones, Clare Austin, Michael J Taggart

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University of Manchester

Research output: Contribution to journal › Article (journal) › peer-review

31 Citations (Scopus)

Abstract

OBJECTIVE: A close association of caveolae and sarcoplasmic reticulum (SR) has been suggested to be important for contractile activation of smooth muscle. Here, we investigate the presence of such arrangements in pressurised resistance arteries and examine the influence of two agents purported to disrupt caveolae and/or SR conformations by different mechanisms of action.

METHODS: Rat mesenteric small arteries (RMSA) were mounted on a pressure myograph and the functional (lumen diameter and Ca(2+) oscillations) and ultrastructural effects of the phosphatase inhibitor calyculin-A (cal-A), or the cholesterol binding agent methyl-beta-cyclodextrin (mbetacd), examined by light and electron microscopy.

RESULTS: Smooth muscle cells of RMSA exhibited a prominent peripheral SR that often encircled individual caveolae. The peripheral SR on occasion was observed to make contact with centrally located SR allowing for a structural association of caveoale-SR-myofilaments. Cal-A maximally constricted RMSA and disrupted the regular SR-caveolae appearance such that concentrated swirls of SR not enveloping caveolae were evident. Mbetacd treatment, in contrast, inhibited agonist contractility and reduced the appearance of caveolae whilst peripheral SR apposition to the plasmalemma could still be observed. Treatment with either agent inhibited agonist-mediated smooth muscle Ca(2+) oscillations.

CONCLUSION: We present data that supports a structural arrangement of caveolae and underlying peripheral SR in smooth muscle cells of pressurised resistance arteries that serves to regulate Ca(2+) oscillations and contractile activation.

Original language	English
Pages (from-to)	825-35
Number of pages	11
Journal	Cardiovascular Research
Volume	69
Issue number	4
DOIs	https://doi.org/10.1016/j.cardiores.2005.12.016
Publication status	Published - 1 Mar 2006

Keywords

Animals
Anticholesteremic Agents/pharmacology
Calcium/metabolism
Caveolae/metabolism
In Vitro Techniques
Mesenteric Arteries
Microscopy, Electron
Muscle Contraction/drug effects
Myocytes, Smooth Muscle/drug effects
Myography
Oxazoles/pharmacology
Phosphoric Monoester Hydrolases/antagonists & inhibitors
Rats
Sarcoplasmic Reticulum/drug effects
beta-Cyclodextrins/pharmacology

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10.1016/j.cardiores.2005.12.016

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@article{49d1aac69b174a7f8159d67e08d21334,

title = "Caveolae and sarcoplasmic reticular coupling in smooth muscle cells of pressurised arteries: the relevance for Ca2+ oscillations and tone",

abstract = "OBJECTIVE: A close association of caveolae and sarcoplasmic reticulum (SR) has been suggested to be important for contractile activation of smooth muscle. Here, we investigate the presence of such arrangements in pressurised resistance arteries and examine the influence of two agents purported to disrupt caveolae and/or SR conformations by different mechanisms of action.METHODS: Rat mesenteric small arteries (RMSA) were mounted on a pressure myograph and the functional (lumen diameter and Ca(2+) oscillations) and ultrastructural effects of the phosphatase inhibitor calyculin-A (cal-A), or the cholesterol binding agent methyl-beta-cyclodextrin (mbetacd), examined by light and electron microscopy.RESULTS: Smooth muscle cells of RMSA exhibited a prominent peripheral SR that often encircled individual caveolae. The peripheral SR on occasion was observed to make contact with centrally located SR allowing for a structural association of caveoale-SR-myofilaments. Cal-A maximally constricted RMSA and disrupted the regular SR-caveolae appearance such that concentrated swirls of SR not enveloping caveolae were evident. Mbetacd treatment, in contrast, inhibited agonist contractility and reduced the appearance of caveolae whilst peripheral SR apposition to the plasmalemma could still be observed. Treatment with either agent inhibited agonist-mediated smooth muscle Ca(2+) oscillations.CONCLUSION: We present data that supports a structural arrangement of caveolae and underlying peripheral SR in smooth muscle cells of pressurised resistance arteries that serves to regulate Ca(2+) oscillations and contractile activation.",

keywords = "Animals, Anticholesteremic Agents/pharmacology, Calcium/metabolism, Caveolae/metabolism, In Vitro Techniques, Mesenteric Arteries, Microscopy, Electron, Muscle Contraction/drug effects, Myocytes, Smooth Muscle/drug effects, Myography, Oxazoles/pharmacology, Phosphoric Monoester Hydrolases/antagonists & inhibitors, Rats, Sarcoplasmic Reticulum/drug effects, beta-Cyclodextrins/pharmacology",

author = "Linda Shaw and Sweeney, {Michele A} and O'Neill, {Stephen C} and Jones, {Carolyn J P} and Clare Austin and Taggart, {Michael J}",

year = "2006",

month = mar,

day = "1",

doi = "10.1016/j.cardiores.2005.12.016",

language = "English",

volume = "69",

pages = "825--35",

journal = "Cardiovascular Research",

issn = "0008-6363",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Caveolae and sarcoplasmic reticular coupling in smooth muscle cells of pressurised arteries

T2 - the relevance for Ca2+ oscillations and tone

AU - Shaw, Linda

AU - Sweeney, Michele A

AU - O'Neill, Stephen C

AU - Jones, Carolyn J P

AU - Austin, Clare

AU - Taggart, Michael J

PY - 2006/3/1

Y1 - 2006/3/1

N2 - OBJECTIVE: A close association of caveolae and sarcoplasmic reticulum (SR) has been suggested to be important for contractile activation of smooth muscle. Here, we investigate the presence of such arrangements in pressurised resistance arteries and examine the influence of two agents purported to disrupt caveolae and/or SR conformations by different mechanisms of action.METHODS: Rat mesenteric small arteries (RMSA) were mounted on a pressure myograph and the functional (lumen diameter and Ca(2+) oscillations) and ultrastructural effects of the phosphatase inhibitor calyculin-A (cal-A), or the cholesterol binding agent methyl-beta-cyclodextrin (mbetacd), examined by light and electron microscopy.RESULTS: Smooth muscle cells of RMSA exhibited a prominent peripheral SR that often encircled individual caveolae. The peripheral SR on occasion was observed to make contact with centrally located SR allowing for a structural association of caveoale-SR-myofilaments. Cal-A maximally constricted RMSA and disrupted the regular SR-caveolae appearance such that concentrated swirls of SR not enveloping caveolae were evident. Mbetacd treatment, in contrast, inhibited agonist contractility and reduced the appearance of caveolae whilst peripheral SR apposition to the plasmalemma could still be observed. Treatment with either agent inhibited agonist-mediated smooth muscle Ca(2+) oscillations.CONCLUSION: We present data that supports a structural arrangement of caveolae and underlying peripheral SR in smooth muscle cells of pressurised resistance arteries that serves to regulate Ca(2+) oscillations and contractile activation.

AB - OBJECTIVE: A close association of caveolae and sarcoplasmic reticulum (SR) has been suggested to be important for contractile activation of smooth muscle. Here, we investigate the presence of such arrangements in pressurised resistance arteries and examine the influence of two agents purported to disrupt caveolae and/or SR conformations by different mechanisms of action.METHODS: Rat mesenteric small arteries (RMSA) were mounted on a pressure myograph and the functional (lumen diameter and Ca(2+) oscillations) and ultrastructural effects of the phosphatase inhibitor calyculin-A (cal-A), or the cholesterol binding agent methyl-beta-cyclodextrin (mbetacd), examined by light and electron microscopy.RESULTS: Smooth muscle cells of RMSA exhibited a prominent peripheral SR that often encircled individual caveolae. The peripheral SR on occasion was observed to make contact with centrally located SR allowing for a structural association of caveoale-SR-myofilaments. Cal-A maximally constricted RMSA and disrupted the regular SR-caveolae appearance such that concentrated swirls of SR not enveloping caveolae were evident. Mbetacd treatment, in contrast, inhibited agonist contractility and reduced the appearance of caveolae whilst peripheral SR apposition to the plasmalemma could still be observed. Treatment with either agent inhibited agonist-mediated smooth muscle Ca(2+) oscillations.CONCLUSION: We present data that supports a structural arrangement of caveolae and underlying peripheral SR in smooth muscle cells of pressurised resistance arteries that serves to regulate Ca(2+) oscillations and contractile activation.

KW - Animals

KW - Anticholesteremic Agents/pharmacology

KW - Calcium/metabolism

KW - Caveolae/metabolism

KW - In Vitro Techniques

KW - Mesenteric Arteries

KW - Microscopy, Electron

KW - Muscle Contraction/drug effects

KW - Myocytes, Smooth Muscle/drug effects

KW - Myography

KW - Oxazoles/pharmacology

KW - Phosphoric Monoester Hydrolases/antagonists & inhibitors

KW - Rats

KW - Sarcoplasmic Reticulum/drug effects

KW - beta-Cyclodextrins/pharmacology

U2 - 10.1016/j.cardiores.2005.12.016

DO - 10.1016/j.cardiores.2005.12.016

M3 - Article (journal)

C2 - 16464442

SN - 0008-6363

VL - 69

SP - 825

EP - 835

JO - Cardiovascular Research

JF - Cardiovascular Research

IS - 4

ER -

Caveolae and sarcoplasmic reticular coupling in smooth muscle cells of pressurised arteries: the relevance for Ca2+ oscillations and tone

Abstract

Keywords

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