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 L. Thornburg, Zhao Wang

    Research output: Contribution to journalArticle

    17 Scopus citations

    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

    Keywords

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

    ASJC Scopus subject areas

    • Biochemistry
    • Pharmacology

    Fingerprint Dive into the research topics of 'Sarcoplasmic reticulum Ca<sup>2+</sup> release channel ryanodine receptor (RyR<sub>2</sub>) plays a crucial role in aconitine-induced arrhythmias'. Together they form a unique fingerprint.

  • Cite this