Involvement of nonselective cation channels in the depolarisation initiating vasomotion

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

    Research output: Contribution to journalArticlepeer-review


    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 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.
    Original languageEnglish
    Pages (from-to)536-543
    JournalClinical and Experimental Pharmacology and Physiology
    Issue number5-June
    Publication statusPublished - 2010


    Dive into the research topics of 'Involvement of nonselective cation channels in the depolarisation initiating vasomotion'. Together they form a unique fingerprint.

    Cite this