title: Do TRPC-like currents and G protein-coupled receptors interact to facilitate myogenic tone development?
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.
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain and Libin Cardiovascular Institutes, University of Calgary, Alberta, Canada.
authors.forename: Yana
authors.initials: Y
authors.lastname: Anfinogenova
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Brett
authors.forename: Michael P
authors.initials: MP
authors.lastname: Walsh
authors.forename: Osama F
authors.initials: OF
authors.lastname: Harraz
authors.forename: Donald G
authors.initials: DG
authors.lastname: Welsh
mesh_terms: D000818:Animals; D020771:Anterior Cerebral Artery / Q000502:physiology; D055724:Electrophysiological Phenomena; D005260:Female; D007473:Ion Channels / Q000502:physiology; D008465:Mechanoreceptors / Q000502:physiology; D009129:Muscle Tonus / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D050052:TRPC Cation Channels; D014662:Vasoconstrictor Agents