The Journal of Membrane Biology

, Volume 198, Issue 2, pp 95–101

Membrane Cholesterol Regulates Smooth Muscle Phasic Contraction

  • E. B. Babiychuk
  • R. D. Smith
  • T. Burdyga
  • V. S. Babiychuk
  • S. Wray
  • A. Draeger
Article

Abstract

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.

Keywords

Membrane segregation Caveolae Raft microdomain Ca2+ Sarcolemma Ion channels 

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • E. B. Babiychuk
    • 1
    • 2
  • R. D. Smith
    • 1
  • T. Burdyga
    • 1
  • V. S. Babiychuk
    • 3
  • S. Wray
    • 1
  • A. Draeger
    • 2
  1. 1.Department of Cell Biology, Institute of AnatomyUniversity of BernSwitzerland
  2. 2.Department of PhysiologyThe University of LiverpoolUK
  3. 3.Department of BiophysicsKiev Taras Shevchenko UniversityKievUkraine

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