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Does G‐protein Coupled Receptor Activation Enhance Cerebral Arterial Mechanosensitivity
Author(s) -
Anfinogenova Yana,
Welsh Suzanne E Brett,
Welsh Donald G
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1024.19
Subject(s) - trpc , trpc3 , trpc5 , chemistry , myograph , trpc1 , amiloride , cerebral arteries , niflumic acid , apamin , dids , g protein coupled receptor , transient receptor potential channel , medicine , receptor , microbiology and biotechnology , endocrinology , biology , biochemistry , potassium channel , vasodilation , organic chemistry , membrane , sodium
This study determined whether the mechano‐sensitivity of a TRPC current in cerebral arterial smooth muscle could be enhanced by G‐protein coupled receptors (GPCRs) in a manner that facilitates myogenic tone development. An initial RT‐PCR analysis revealed the expression of TRPC1, 3, 6 & 7 mRNA in smooth muscle cells isolated from anterior cerebral arteries. Whole cell patch clamp electrophysiology subsequently confirmed the presence of a doubly rectifying current that displayed properties characteristic of a heteromultimeric TRPC3/6/7 channel. In particular, this non‐selective cation current was blocked by micromolar trivalents (Gd 3+ and Ln 3+ ) but insensitive to Cl − inhibitors (DIDS, niflumic acid, tamoxifen and flufenamic acid) and amiloride. GPCR agonists (UTP and U46619) augmented the activity of the TRPC‐like current as did a mechano‐stimulus like hyposmotic challenge (300 to 200 mOsm). While GPCR agonists can directly modulate TRPC‐like currents, this study found no evidence to suggest that they facilitate mechano‐sensitivity. The preceding findings were consistent with functional work which revealed that while GPCR agonists cause constriction, they do not enhance the myogenic reactivity of cerebral arteries. In closing, our findings suggest, in contrast to previous HEK expression studies, that GCPR activation does not enhance the mechano‐sensitivity of TRPC‐like currents nor the myogenic sensitivity of intact cerebral arteries. Supported by NSERC.