Do TRPC-like currents and G protein-coupled receptors interact to facilitate myogenic tone development?

Yana Anfinogenova, Suzanne E. Brett, Michael P. Walsh, Osama F. Harraz, Donald G. Welsh

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25 Citations (Scopus)

Abstract

The objective of this study was to determine whether G q/11-coupled receptor activation can enhance the mechanosensitivity of a canonical transient receptor potential (TRPC)-like current and consequently the myogenic responsiveness of rat anterior cerebral arteries. Initial patch-clamp experiments revealed the presence of a basal cation current in isolated smooth muscle cells that displayed evidence of double rectification, which was blocked by trivalent cations (Gd 3+ and La 3+). PCR analysis identified the expression of TRPC1, 3, 6 and 7 mRNA and, characteristic of TRPC-like current, the whole-cell conductance was insensitive to a Na +-dependent transport (amiloride), TRP vanilloid (ruthenium red), and chloride channel (DIDS, niflumic acid, and flufenamate) inhibitors. One notable exception was tamoxifen, which elicited a dual effect, blocking or activating the TRPC-like current at 1 and 10 μM, respectively. This TRPC-like current was augmented by constrictor agonists (uridine 5'-triphosphate and U46619) or hyposmotic challenge (303 to 223 mOsm/l), a mechanical stimulus. Although each stimulus was effective alone, smooth muscle cells pretreated with agonist did not augment the whole-cell response to hyposmotic challenge. Consistent with these electrophysiological recordings, functional experiments revealed that neither UTP nor U46619 enhanced the sensitivity of intact cerebral arteries to hyposmotic challenge or elevated intravascular pressure. In summary, this study found no evidence that G q/11-coupled receptor activation augments the mechanosensitivity of a TRPC-like current and consequently the myogenic responsiveness of anterior cerebral arteries.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number4
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

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Keywords

  • Intravascular pressure
  • Myogenic response
  • Transient receptor potential canonical channels
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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