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
Hauptverfasser: Potocnik, Simon J., Jenkins, Nicole, Murphy, Timothy V., Hill, Michael A.
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creator Potocnik, Simon J.
Jenkins, Nicole
Murphy, Timothy V.
Hill, Michael A.
description 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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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.</description><identifier>ISSN: 1018-1172</identifier><identifier>EISSN: 1423-0135</identifier><identifier>DOI: 10.1159/000101451</identifier><identifier>PMID: 17406121</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>Animals ; Arterioles - drug effects ; Arterioles - physiology ; Arterioles - ultrastructure ; beta-Cyclodextrins - pharmacology ; Biological and medical sciences ; Calcium - metabolism ; Calcium Signaling - drug effects ; Calcium Signaling - physiology ; Carcinogens - pharmacology ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cell Membrane - ultrastructure ; Cholesterol - metabolism ; Fundamental and applied biological sciences. Psychology ; In Vitro Techniques ; Male ; Microscopy, Electron ; Muscle Contraction - drug effects ; Muscle Contraction - physiology ; Muscle, Skeletal - blood supply ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - physiology ; Muscle, Smooth, Vascular - ultrastructure ; Pressure ; Rats ; Rats, Sprague-Dawley ; Research Paper ; Vasoconstriction - drug effects ; Vasoconstriction - physiology ; Vertebrates: cardiovascular system</subject><ispartof>Journal of vascular research, 2007-01, Vol.44 (4), p.292-302</ispartof><rights>2007 S. 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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. 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Psychology</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Microscopy, Electron</subject><subject>Muscle Contraction - drug effects</subject><subject>Muscle Contraction - physiology</subject><subject>Muscle, Skeletal - blood supply</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - physiology</subject><subject>Muscle, Smooth, Vascular - ultrastructure</subject><subject>Pressure</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Research Paper</subject><subject>Vasoconstriction - drug effects</subject><subject>Vasoconstriction - physiology</subject><subject>Vertebrates: cardiovascular system</subject><issn>1018-1172</issn><issn>1423-0135</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpN0cFu1DAQBmALUdFSOHBHyBeQOKR4nDiJj1UosFIrkArnaOJMtqZOvNiJaF-EB-FBeCa83VXbk23pm_ntMWOvQJwAKP1BCAECCgVP2BEUMs8E5Opp2guoM4BKHrLnMf5MqtB1-YwdQlWIEiQcsT8XNHYBJ-LNlXcUZwre8Y-0cTRbP_Hfdr7i__5mza1xvqebOdiJr8YN2hD5t0AxLoGy1dQvhnre-GkOaO4qcUpndMYuI7-06wmds9Oab8ujdzgnfnlNKQYdv1iiccRPQ4q322u8YAcDukgv9-sx-_Hp7HvzJTv_-nnVnJ5nJi_VnA2gc6URu74cQFXYUdWBAuxRlVgXmAuBne5kTqiEQej10JVSatFjMaiyyI_Zu13fTfC_lvT8drTRkHNpIn6JrRRagtaQ4PsdNMHHGGhoN8GOGG5bEO32E9r7T0j2zb7p0o3UP8j91BN4uwcYDbohzd_Y-ODqGqpa6uRe79w1hjWFR5F3Of8BvdubSg</recordid><startdate>20070101</startdate><enddate>20070101</enddate><creator>Potocnik, Simon J.</creator><creator>Jenkins, Nicole</creator><creator>Murphy, Timothy V.</creator><creator>Hill, Michael A.</creator><general>Karger</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope></search><sort><creationdate>20070101</creationdate><title>Membrane Cholesterol Depletion with β-Cyclodextrin Impairs Pressure-Induced Contraction and Calcium Signalling in Isolated Skeletal Muscle Arterioles</title><author>Potocnik, Simon J. ; Jenkins, Nicole ; Murphy, Timothy V. ; Hill, Michael A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-f19359aabd6f157abe7b151ada56a84a300ab9b23ea50ca1d9fb62290da4f5643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Arterioles - drug effects</topic><topic>Arterioles - physiology</topic><topic>Arterioles - ultrastructure</topic><topic>beta-Cyclodextrins - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Calcium Signaling - drug effects</topic><topic>Calcium Signaling - physiology</topic><topic>Carcinogens - pharmacology</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Membrane - ultrastructure</topic><topic>Cholesterol - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Microscopy, Electron</topic><topic>Muscle Contraction - drug effects</topic><topic>Muscle Contraction - physiology</topic><topic>Muscle, Skeletal - blood supply</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - physiology</topic><topic>Muscle, Smooth, Vascular - ultrastructure</topic><topic>Pressure</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Research Paper</topic><topic>Vasoconstriction - drug effects</topic><topic>Vasoconstriction - physiology</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Potocnik, Simon J.</creatorcontrib><creatorcontrib>Jenkins, Nicole</creatorcontrib><creatorcontrib>Murphy, Timothy V.</creatorcontrib><creatorcontrib>Hill, Michael A.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><jtitle>Journal of vascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Potocnik, Simon J.</au><au>Jenkins, Nicole</au><au>Murphy, Timothy V.</au><au>Hill, Michael A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Membrane Cholesterol Depletion with β-Cyclodextrin Impairs Pressure-Induced Contraction and Calcium Signalling in Isolated Skeletal Muscle Arterioles</atitle><jtitle>Journal of vascular research</jtitle><addtitle>J Vasc Res</addtitle><date>2007-01-01</date><risdate>2007</risdate><volume>44</volume><issue>4</issue><spage>292</spage><epage>302</epage><pages>292-302</pages><issn>1018-1172</issn><eissn>1423-0135</eissn><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. 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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.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>17406121</pmid><doi>10.1159/000101451</doi><tpages>11</tpages></addata></record>
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subjects Animals
Arterioles - drug effects
Arterioles - physiology
Arterioles - ultrastructure
beta-Cyclodextrins - pharmacology
Biological and medical sciences
Calcium - metabolism
Calcium Signaling - drug effects
Calcium Signaling - physiology
Carcinogens - pharmacology
Cell Membrane - drug effects
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cholesterol - metabolism
Fundamental and applied biological sciences. Psychology
In Vitro Techniques
Male
Microscopy, Electron
Muscle Contraction - drug effects
Muscle Contraction - physiology
Muscle, Skeletal - blood supply
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - physiology
Muscle, Smooth, Vascular - ultrastructure
Pressure
Rats
Rats, Sprague-Dawley
Research Paper
Vasoconstriction - drug effects
Vasoconstriction - physiology
Vertebrates: cardiovascular system
title Membrane Cholesterol Depletion with β-Cyclodextrin Impairs Pressure-Induced Contraction and Calcium Signalling in Isolated Skeletal Muscle Arterioles
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