Membrane cholesterol depletion with beta-cyclodextrin impairs pressure-induced contraction and calcium signalling in isolated skeletal muscle arterioles

Potocnik, S, Jenkins, N, Murphy, T and Hill, M 2007, 'Membrane cholesterol depletion with beta-cyclodextrin impairs pressure-induced contraction and calcium signalling in isolated skeletal muscle arterioles', Journal Of Vascular Research, vol. 44, no. 4, pp. 292-302.


Document type: Journal Article
Collection: Journal Articles

Title Membrane cholesterol depletion with beta-cyclodextrin impairs pressure-induced contraction and calcium signalling in isolated skeletal muscle arterioles
Author(s) Potocnik, S
Jenkins, N
Murphy, T
Hill, M
Year 2007
Journal name Journal Of Vascular Research
Volume number 44
Issue number 4
Start page 292
End page 302
Total pages 11
Publisher Karger
Abstract OBJECTIVE - Given evidence for clustering of signalling molecules and ion channels in cholesterol- rich membrane domains, the involvement of such structures in arteriolar smooth muscle mechanotransduction was examined. METHOD - To determine the contribution of smooth muscle cholesterol-rich membrane domains to the myogenic response, isolated arterioles were exposed to the cholesterol- depleting agent beta-cyclodextrin (1-10 m M) in the absence and presence of excess exogenous cholesterol. RESULTS - beta-Cyclodextrin significantly impaired pressure-induced vasoconstriction, while excess cholesterol attenuated this effect. Impaired myogenic constriction was evident in de-endothelialized vessels, indicating an action at the level of smooth muscle. beta-Cyclodextrin treatment uncoupled increases in intracellular Ca2+ from myogenic constriction and depleted intracellular Ca2+ stores consistent with a loss of connectivity between plasma membrane and sarcoplasmic reticulum signalling. However, beta-cyclodextrin- treated arterioles showed unaltered constrictor responses to KCl and phenylephrine. Electron microscopy verified that beta-cyclodextrin caused a decrease in caveolae, while confirmation of smooth muscle containing caveolae was obtained by immunostaining for caveolin-1. Viability of beta-cyclodextrin-treated arterioles was confirmed by agonist sensitivity and propidium iodide nuclear staining. CONCLUSION - The data suggest that smooth muscle cholesterol-rich membrane domains contribute to the myogenic response. Further studies are required to determine whether this relates to specific mechanosensory events or generalized alterations in membrane function.
Subject Biomechanics
Keyword(s) Vascular Smooth-Muscle
Capacitative Ca2+ Entry
Cerebral-Arteries
Myogenic Constriction
Plasmalemmal Caveolae
Intraluminal Pressure
Actin Cytoskeleton
Endothelial-Cells
Forced Dilatation
In-Vitro
DOI - identifier 10.1159/000101451
Copyright notice © 2007 S. Karger AG, Basel
ISSN 1018-1172
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