Inhibition of ryanodine binding to sarcoplasmic reticulum vesicles of cardiac muscle by Zn2+ ions

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Using the assay of [3H]ryanodine binding to the sarcoplasmic reticulum, the effect of Zn2+ on ryanodine receptors (RyRs) of cardiac muscle was investigated. There was no obvious change in the binding at [Zn2+]f of less than 0.2 μM. However, a decrease of the binding became significant with raising [Zn2+]f to 0.5 μM. The inhibitory effect of Zn2+ was [Zn2+]f-dependent, with IC50/ZnI of 2.1±0.4 μM (mean±S.D.). Scatchard analysis indicates that both an increase of Kd and a decrease of Bmax were responsible for Zn2+-induced decrease of the binding. The Hill coefficient for this inhibitory effect of Zn2+ was between 0.8 and 1.2. The interactions of the effects of Zn2+ and various modulators of RyR indicate that the inhibitory effect of Zn2+ was mostly mediated through inhibiting Ca2+ activation sites (CaA) on RyR. Since the [Zn2+]f dependence was not clearly changed by [Ca2+]f, the inhibitory effect of Zn2+ may not be due to competition of Zn2+ with Ca2+ for CaA and probably is indirect. The inhibitory effect of Zn2+ could not be antagonized by 2 mM dithiothreitol, a thiol-reducing agent, suggesting that the binding of Zn2+ 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 Zn2+ on ryanodine binding to the sarcoplasmic reticulum of cardiac muscle show several distinct differences. It is indicated that the effect of Zn2+ on RyRs may be isoform-dependent. The physiological significance of the effects of Zn2+ is discussed.

Original languageEnglish (US)
Pages (from-to)83-92
Number of pages10
JournalCellular Physiology and Biochemistry
Volume11
Issue number2
DOIs
StatePublished - Apr 10 2001
Externally publishedYes

Fingerprint

Ryanodine
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum
Myocardium
Ions
Dithiothreitol
Reducing Agents
Sulfhydryl Compounds
Inhibitory Concentration 50
Oxidation-Reduction
Protein Isoforms
Skeletal Muscle

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

Inhibition of ryanodine binding to sarcoplasmic reticulum vesicles of cardiac muscle by Zn2+ ions. / Wang, Hui; Wei, QingQing; Cheng, Xiao Yang; Chen, Ke Ying; Zhu, Pei Hong.

In: Cellular Physiology and Biochemistry, Vol. 11, No. 2, 10.04.2001, p. 83-92.

Research output: Contribution to journalArticle

Wang, Hui ; Wei, QingQing ; Cheng, Xiao Yang ; Chen, Ke Ying ; Zhu, Pei Hong. / Inhibition of ryanodine binding to sarcoplasmic reticulum vesicles of cardiac muscle by Zn2+ ions. In: Cellular Physiology and Biochemistry. 2001 ; Vol. 11, No. 2. pp. 83-92.
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