Reduced Ca2+ spark activity after subarachnoid hemorrhage disables BK channel control of cerebral artery tone

Masayo Koide, Matthew A. Nystoriak, Gayathri Krishnamoorthy, Kevin P. O'Connor, Adrian D. Bonev, Mark T. Nelson, George C. Wellman

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Intracellular Ca2+ release events (Ca2+ sparks) and transient activation of large-conductance Ca2+-activated potassium (BK) channels represent an important vasodilator pathway in the cerebral vasculature. Considering the frequent occurrence of cerebral artery constriction after subarachnoid hemorrhage (SAH), our objective was to determine whether Ca2+ spark and BK channel activity were reduced in cerebral artery myocytes from SAH model rabbits. Using laser scanning confocal microscopy, we observed ∼50% reduction in Ca2+ spark activity, reflecting a decrease in the number of functional Ca2+ spark discharge sites. Patch-clamp electrophysiology showed a similar reduction in Ca2+ spark-induced transient BK currents, without change in BK channel density or single-channel properties. Consistent with a reduction in active Ca2+ spark sites, quantitative real-time PCR and western blotting revealed decreased expression of ryanodine receptor type 2 (RyR-2) and increased expression of the RyR-2-stabilizing protein, FKBP12.6, in the cerebral arteries from SAH animals. Furthermore, inhibitors of Ca2+ sparks (ryanodine) or BK channels (paxilline) constricted arteries from control, but not from SAH animals. This study shows that SAH-induced decreased subcellular Ca2+ signaling events disable BK channel activity, leading to cerebral artery constriction. This phenomenon may contribute to decreased cerebral blood flow and poor outcome after aneurysmal SAH. © 2011 ISCBFM All rights reserved.
    Original languageEnglish
    Pages (from-to)3-16
    Number of pages13
    JournalJournal of Cerebral Blood Flow and Metabolism
    Volume31
    Issue number1
    DOIs
    Publication statusPublished - Jan 2011

    Keywords

    • cerebral aneurysm
    • FKBP12.6
    • potassium channels
    • ryanodine receptors
    • vascular smooth muscle
    • vasospasm

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