Membrane Cholesterol Depletion with β-Cyclodextrin Impairs Pressure-Induced Contraction and Calcium Signalling in Isolated Skeletal Muscle Arterioles
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 do...
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Veröffentlicht in: | Journal of vascular research 2007-01, Vol.44 (4), p.292-302 |
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Sprache: | eng |
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Zusammenfassung: | 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 β-cyclodextrin (1–10 mM) in the absence and presence of excess exogenous cholesterol. Results: β-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. β-Cyclodextrin treatment uncoupled increases in intracellular Ca 2+ from myogenic constriction and depleted intracellular Ca 2+ stores consistent with a loss of connectivity between plasma membrane and sarcoplasmic reticulum signalling. However, β-cyclodextrin-treated arterioles showed unaltered constrictor responses to KCl and phenylephrine. Electron microscopy verified that β-cyclodextrin caused a decrease in caveolae, while confirmation of smooth muscle containing caveolae was obtained by immunostaining for caveolin-1. Viability of β-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. |
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ISSN: | 1018-1172 1423-0135 |
DOI: | 10.1159/000101451 |