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Membrane Cholesterol Regulates Smooth Muscle Phasic Contraction

Babiychuk, E. ; Smith, R. ; Burdyga, T. ; Babiychuk, V. ; Wray, S. ; Draeger, A.

In: The Journal of Membrane Biology, 2004, vol. 198, no. 2, p. 95-101

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    Titel
    • Membrane Cholesterol Regulates Smooth Muscle Phasic Contraction
    Autor
    • Babiychuk, E.. Department of Cell Biology, Institute of Anatomy, University of Bern, Bern 9, 3000, CH, Switzerland
    • Smith, R.. Department of Cell Biology, Institute of Anatomy, University of Bern, Bern 9, 3000, CH, Switzerland
    • Burdyga, T.. Department of Cell Biology, Institute of Anatomy, University of Bern, Bern 9, 3000, CH, Switzerland
    • Babiychuk, V.. Department of Biophysics, Kiev Taras Shevchenko University, 01033, Kiev, Ukraine
    • Wray, S.. Department of Cell Biology, Institute of Anatomy, University of Bern, Bern 9, 3000, CH, Switzerland
    • Draeger, A.. Department of Physiology, The University of Liverpool, Liverpool L69, 3BX, UK
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • The Journal of Membrane Biology, 2004, vol. 198, no. 2, p. 95-101. Springer-Verlag; www.springer-ny.com
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:311093
    Summary
    The regulation of contractile activity in smooth muscle cells involves rapid discrimination and processing of a multitude of simultaneous signals impinging on the membrane before an integrated functional response can be generated. The sarcolemma of smooth muscle cells is segregated into caveolar regions-largely identical with cholesterol-rich membrane rafts—and actin-attachment sites, localized in non-raft, glycerophospholipid regions. Here we demonstrate that selective extraction of cholesterol abolishes membrane segregation and disassembles caveolae. Simultaneous measurements of force and [Ca2+]i in rat ureters demonstrated that extraction of cholesterol resulted in inhibition of both force and intracellular Ca2+ signals. Considering the major structural reorganization of cholesterol-depleted sarcolemma, it is intriguing to note that decreased levels of membrane cholesterol are accompanied by a highly specific inhibition of phasic, but not tonic contractions. This implies that signalling cascades that ultimately lead to either phasic or tonic response may be spatially segregated in the plane of the sarcolemma. Replenishment of cholesterol restores normal contractile behavior. In addition, the tissue function is re-established by inhibiting the large-conductance K+-channel. Sucrose gradient ultracentrifugation in combination with Western blotting analysis demonstrates that its α-subunit is associated with detergent-resistant membranes, suggesting that the channel might be localized within the membrane rafts in vivo. These findings are important in understanding the complex signalling pathways in smooth muscle and conditions such as premature labor and hypertension