Inhibition of ryanodine binding to sarcoplasmic reticulum vesicles of cardiac muscle by Zn 2+ ions

Hui Wang, Qing Qing Wei, Xiao Yang Cheng, Ke Ying Chen, Pei Hong Zhu

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Using the assay of [ 3 H]ryanodine binding to the sarcoplasmic reticulum, the effect of Zn 2+ on ryanodine receptors (RyRs) of cardiac muscle was investigated. There was no obvious change in the binding at [Zn 2+ ] f of less than 0.2 μM. However, a decrease of the binding became significant with raising [Zn 2+ ] f to 0.5 μM. The inhibitory effect of Zn 2+ was [Zn 2+ ] f -dependent, with IC 50/ZnI of 2.1±0.4 μM (mean±S.D.). Scatchard analysis indicates that both an increase of K d and a decrease of B max were responsible for Zn 2+ -induced decrease of the binding. The Hill coefficient for this inhibitory effect of Zn 2+ was between 0.8 and 1.2. The interactions of the effects of Zn 2+ and various modulators of RyR indicate that the inhibitory effect of Zn 2+ was mostly mediated through inhibiting Ca 2+ activation sites (CaA) on RyR. Since the [Zn 2+ ] f dependence was not clearly changed by [Ca 2+ ] f, the inhibitory effect of Zn 2+ may not be due to competition of Zn 2+ with Ca 2+ for CaA and probably is indirect. The inhibitory effect of Zn 2+ could not be antagonized by 2 mM dithiothreitol, a thiol-reducing agent, suggesting that the binding of Zn 2+ ions to RyRs of cardiac muscle is not accompanied by obvious change of redox state of the RyRs. In comparison with that seen in skeletal muscle [3], the effects of Zn 2+ on ryanodine binding to the sarcoplasmic reticulum of cardiac muscle show several distinct differences. It is indicated that the effect of Zn 2+ on RyRs may be isoform-dependent. The physiological significance of the effects of Zn 2+ is discussed.

Original languageEnglish (US)
Pages (from-to)83-92
Number of pages10
JournalCellular Physiology and Biochemistry
Volume11
Issue number2
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Binding assay
  • Ca
  • Caffeine
  • Dithiotheitol
  • Ryanodine receptor
  • Zn

ASJC Scopus subject areas

  • Physiology

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