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. Orlov

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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 Ca 2+ o. Thirty minutes preincubation with bumetanide, a potent Na+,K+,Cl- cotransport (NKCC) inhibitor, decreased Cl- i 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 Cl- i-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.

Original languageEnglish
Pages (from-to)42-55
Number of pages14
JournalPflugers Archiv European Journal of Physiology
Volume449
Issue number1
DOIs
Publication statusPublished - Oct 2004
Externally publishedYes

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Keywords

  • Ca channels
  • Cell volume
  • Contraction
  • Intracellular Cl
  • Na,K,2Cl cotransport
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology

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