TRPV2 Is a Component of Osmotically Sensitive Cation Channels in Murine Aortic Myocytes

Katsuhiko Muraki, Yuko Iwata, Yuki Katanosaka, Tomohiro Ito, Susumu Ohya, Munekazu Shigekawa, Yuji Imaizumi

Research output: Contribution to journalArticlepeer-review

378 Citations (Scopus)

Abstract

Changes in membrane tension resulting from membrane stretch represent one of the key elements in blood flow regulation in vascular smooth muscle. However, the molecular mechanisms involved in the regulation of membrane stretch remain unclear. In this study, we provide evidence that a vanilloid receptor (TRPV) homologue, TRPV2 is expressed in vascular smooth muscle cells, and demonstrate that it can be activated by membrane stretch. Cell swelling caused by hypotonic solutions activated a nonselective cation channel current (NSCC) and elevated intracellular Ca2+ ([Ca2+]i) in freshly isolated cells from mouse aorta. Both of these signals were blocked by ruthenium red, an effective blocker of TRPVs. The absence of external Ca 2+ abolished this increase in [Ca2+]i caused by the hypotonic stimulation and reduced the activation of NSCC. Significant immunoreactivity to mouse TRPV2 protein was detected in single mouse aortic myocytes. Moreover, the expression of TRPV2 was found in mesenteric and basilar arterial myocytes. Treatment of mouse aorta with TRPV2 antisense oligonucleotides resulted in suppression of hypotonic stimulation-induced activation of NSCC and elevation of [Ca2+]i as well as marked inhibition of TRPV2 protein expression. In Chinese hamster ovary K1 (CHO) cells transfected with TRPV2 cDNA (TRPV2-CHO), application of membrane stretch through the recording pipette and hypotonic stimulation consistently activated single NSCC. Moreover, stretch of TRPV2-CHO cells cultured on an elastic silicon membrane significantly elevated [Ca2+]i. These results provide a strong basis for our purpose that endogenous TRPV2 in mouse vascular myocytes functions as a novel and important stretch sensor in vascular smooth muscles.

Original languageEnglish
Pages (from-to)829-838
Number of pages10
JournalCirculation research
Volume93
Issue number9
DOIs
Publication statusPublished - Oct 31 2003
Externally publishedYes

Keywords

  • Membrane stretch
  • Mouse aorta
  • TRPV2
  • Vanilloid receptor
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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