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Involvement of nonselective cation channels in the depolarisation initiating vasomotion

Wolfle, Stephanie; Navarro-Gonzalez, Manuel; Grayson, Hilton; Stricker, Christian; Hill, Caryl

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1. Coordinated oscillations in diameter occur spontaneously in cerebral vessels and depend on the opening of voltage dependent calcium channels. However, the mechanism that induces the initial depolarisation has remained elusive. We investigated the involvement of canonical transient receptor potential (TRPC) channels, which encode nonselective cation channels passing Na+ and Ca2+ currents, by measuring changes in diameter, intracellular Ca2+ and membrane potential in branches of juvenile rat...[Show more]

dc.contributor.authorWolfle, Stephanie
dc.contributor.authorNavarro-Gonzalez, Manuel
dc.contributor.authorGrayson, Hilton
dc.contributor.authorStricker, Christian
dc.contributor.authorHill, Caryl
dc.date.accessioned2015-12-08T22:14:14Z
dc.identifier.issn0305-1870
dc.identifier.urihttp://hdl.handle.net/1885/30145
dc.description.abstract1. Coordinated oscillations in diameter occur spontaneously in cerebral vessels and depend on the opening of voltage dependent calcium channels. However, the mechanism that induces the initial depolarisation has remained elusive. We investigated the involvement of canonical transient receptor potential (TRPC) channels, which encode nonselective cation channels passing Na+ and Ca2+ currents, by measuring changes in diameter, intracellular Ca2+ and membrane potential in branches of juvenile rat basilar arteries. 2. Removal of extracellular Ca2+ abolished vasomotion and relaxed arteries, but paradoxically produced depolarisation. 3. Decrease in temperature to 24°C or inhibition of phospholipase C (PLC) abolished vasomotion, hyperpolarised and relaxed arteries and decreased intracellular Ca2+. 4. Reduction in the driving force for Na+ through decrease in extracellular Na+ produced similar effects and prevented the depolarisation elicited by removal of extracellular Ca2+. 5. Nonselective TRP channel blockers, SKF96365 and gadolinium, mimicked the effects of inhibition of the PLC pathway. 6. Depolarisation of vessels in which TRP channels were blocked with SKF96365 reinstated vascular tone and vasomotion. 7. Quantitative polymerase chain reaction revealed TRPC1 as the predominantly expressed TRPC subtype. 8. Incubation with a function blocking TRPC1 antibody delayed the onset of vasomotion. 9. We conclude that nonselective cation channels contribute to vasoconstriction and vasomotion of cerebral vessels by providing an Na+-induced depolarisation that activates voltage dependent calcium channels. Our antibody data suggest the involvement of TRPC1 channels that might provide a target for treatment of therapy-refractory vasospasm.
dc.publisherBlackwell Science Asia
dc.sourceClinical and Experimental Pharmacology and Physiology
dc.subjectKeywords: 1 [2 (4 methoxyphenyl) 2 [3 (4 methoxyphenyl)propoxy]ethyl] 1h imidazole; calcium channel; calcium ion; gadolinium; phospholipase C; sodium channel; sodium ion; transient receptor potential channel 1; transient receptor potential channel affecting agent; Cerebral; Depolarisation; Nonselective cation channels; Resistance artery; TRPC1; Vasomotion
dc.titleInvolvement of nonselective cation channels in the depolarisation initiating vasomotion
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume1
dc.date.issued2010
local.identifier.absfor111501 - Basic Pharmacology
local.identifier.ariespublicationu4693331xPUB71
local.type.statusPublished Version
local.contributor.affiliationWolfle, Stephanie, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationNavarro-Gonzalez, Manuel, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGrayson, Hilton, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationStricker, Christian, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationHill, Caryl, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue1
local.bibliographicCitation.startpage1
local.bibliographicCitation.lastpage27
local.identifier.doi10.1111/j.1440-1681.2010.05350.x
dc.date.updated2016-02-24T11:18:11Z
local.identifier.scopusID2-s2.0-77951140700
CollectionsANU Research Publications

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