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Pflügers Archiv

, Volume 449, Issue 1, pp 42–55 | Cite as

Cell-volume-dependent vascular smooth muscle contraction: role of Na+, K+, 2Cl cotransport, intracellular Cl and L-type Ca2+ channels

  • Yana J. Anfinogenova
  • Mikhail B. Baskakov
  • Igor V. Kovalev
  • Alexander A. Kilin
  • Nickolai O. Dulin
  • Sergei N. OrlovEmail author
Cell and Molecular Physiology

Abstract

This study elucidates the role of cell volume in contractions of endothelium-denuded vascular smooth muscle rings (VSMR) from the rat aorta. We observed that hyposmotic swelling as well as hyper- and isosmotic shrinkage led to VSMR contractions. Swelling-induced contractions were accompanied by activation of Ca2+ influx and were abolished by nifedipine and verapamil. In contrast, contractions of shrunken cells were insensitive to the presence of L-type channel inhibitors and occurred in the absence of Ca2+o. Thirty minutes preincubation with bumetanide, a potent Na+,K+,Cl cotransport (NKCC) inhibitor, decreased Cli content, nifedipine-sensitive 45Ca uptake and contractions triggered by modest depolarization ([K+]o=36 mM). Elevation of [K+]o to 66 mM completely abolished the effect of bumetanide on these parameters. Bumetanide almost completely abrogated phenylephrine-induced contraction, partially suppressed contractions triggered by hyperosmotic shrinkage, but potentiated contractions of isosmotically shrunken VSMR. Our results suggest that bumetanide suppresses contraction of modestly depolarized cells via NKCC inhibition and Cli-mediated membrane hyperpolarization, whereas augmented contraction of isosmotically shrunken VSMR by bumetanide is a consequence of suppression of NKCC-mediated regulatory volume increase. The mechanism of bumetanide inhibition of contraction of phenylephrine-treated and hyperosmotically shrunken VSMR should be examined further.

Keywords

Ca2+ channels Cell volume Contraction Intracellular Cl Na+,K+,2Cl cotransport Smooth muscle 

Notes

Acknowledgements

This work was supported by grants from the Heart and Stroke Foundation of Canada, and the INTAS Young Scientist Fellowship (YSF 2001/2-0168). The editorial assistance help of Ovid Da Silva, Editor, Research Support Office, Research Centre, CHUM, is appreciated.

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Copyright information

© Springer-Verlag  2004

Authors and Affiliations

  • Yana J. Anfinogenova
    • 1
  • Mikhail B. Baskakov
    • 1
  • Igor V. Kovalev
    • 1
  • Alexander A. Kilin
    • 1
  • Nickolai O. Dulin
    • 2
  • Sergei N. Orlov
    • 3
    • 4
    Email author
  1. 1.Department of Biophysics and Functional DiagnosticsSiberian State Medical UniversityTomskRussia
  2. 2.Department of MedicineUniversity of ChicagoChicagoUSA
  3. 3.Faculty of BiologyM.V. Lomonosov Moscow State UniversityMoscowRussia
  4. 4.Research CentreUniversity of Montreal Hospital (CHUM-Hôtel-Dieu)MontrealCanada

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