Sarcoplasmic reticulum Ca2+ release channel ryanodine receptor (RyR2) plays a crucial role in aconitine-induced arrhythmias

Min Fu, Ru Xin Li, Li Fan, Guo Wei He, Kent Thornburg, Zhao Wang

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    The present study established a model of RyR2 knockdown cardiomyocytes and elucidated the role of RyR2 in aconitine-induced arrhythmia. Cardiomyocytes were obtained from hearts of neonatal Sprague-Dawlay rats. siRNAs were used to down-regulate RyR2 expression. Reduction of RyR2 expression was documented by RT-PCR, western blot, and immunofluorescence. Ca2+ signals were investigated by measuring the relative intracellular Ca2+ concentration, spontaneous Ca2+ oscillations, caffeine-induced Ca2+ release, and L-type Ca2+ currents. In normal cardiomyocytes, steady and periodic spontaneous Ca2+ oscillations were observed, and the baseline [Ca2+]i remained at the low level. Exposure to 3 μM aconitine increased the frequency and decreased the amplitude of Ca2+ oscillations; the baseline [Ca2+]i and the level of caffeine-induced Ca2+ release were increased but the L-type Ca2+ currents were inhibited after application of 3 μM aconitine for 5 min. In RyR2 knockdown cardiomyocytes, the steady and periodic spontaneous Ca2+ oscillations almost disappeared, but were re-induced by aconitine without affecting the baseline [Ca2+]i level; the level of caffeine-induced Ca2+ release was increased but L-type Ca2+ currents were inhibited. Alterations of RyR2 are important consequences of aconitine-stimulation and activation of RyR2 appear to have a direct relationship with aconitine-induced arrhythmias. The present study demonstrates a potential method for preventing aconitine-induced arrhythmias by inhibiting Ca2+ leakage through the sarcoplasmic reticulum RyR2 channel.

    Original languageEnglish (US)
    Pages (from-to)2147-2156
    Number of pages10
    JournalBiochemical Pharmacology
    Volume75
    Issue number11
    DOIs
    StatePublished - Jun 1 2008

    Fingerprint

    Aconitine
    Ryanodine Receptor Calcium Release Channel
    Sarcoplasmic Reticulum
    Cardiac Arrhythmias
    Cardiac Myocytes
    Caffeine
    Fluorescent Antibody Technique
    Rats
    Down-Regulation
    Western Blotting
    Chemical activation
    Polymerase Chain Reaction

    Keywords

    • Aconitine
    • Arrhythmia
    • Excitation-contraction coupling
    • Knockdown
    • RyR

    ASJC Scopus subject areas

    • Pharmacology

    Cite this

    Sarcoplasmic reticulum Ca2+ release channel ryanodine receptor (RyR2) plays a crucial role in aconitine-induced arrhythmias. / Fu, Min; Li, Ru Xin; Fan, Li; He, Guo Wei; Thornburg, Kent; Wang, Zhao.

    In: Biochemical Pharmacology, Vol. 75, No. 11, 01.06.2008, p. 2147-2156.

    Research output: Contribution to journalArticle

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