Copyright © 2006, European Society of Cardiology
Caveolae and sarcoplasmic reticular coupling in smooth muscle cells of pressurised arteries: The relevance for Ca2+ oscillations and tone
aDivision of Cardiovascular and Endocrine Sciences, University of Manchester, Great Britain, United Kingdom
bDivision of Human Development, University of Manchester, Great Britain, United Kingdom
* Corresponding author. Smooth Muscle Physiology Group, Division of Cardiac and Endocrine Sciences, Department of Medicine, University of Manchester, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, United Kingdom. Tel.: +44 161 276 5469; fax: +44 161 276 8433. Email address: Michael.j.Taggart{at}manchester.ac.uk
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 Ca2+ oscillations) and ultrastructural effects of the phosphatase inhibitor calyculin-A (cal-A), or the cholesterol binding agent methyl-β-cyclodextrin (mβcd), 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. Mβcd 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 Ca2+ 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 Ca2+ oscillations and contractile activation.
KEYWORDS Caveolae; Sarcoplasmic reticulum; Resistance arteries; Ca oscillations
Time for primary review 29 days
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