Coordinated regulation of murine cardiomyocyte contractility by nanomolar (-)-epigallocatechin-3-gallate, the major green tea catechin

Wei Feng, Hyun Seok Hwang, Dmytro O. Kryshtal, Tao Yang, Isela T. Padilla, Asheesh K. Tiwary, Birgit Puschner, Isaac N Pessah, Björn C. Knollmann

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Green tea polyphenolic catechins exhibit biological activity in a wide variety of cell types. Although reports in the lay and scientific literature suggest therapeutic potential for improving cardiovascular health, the underlying molecular mechanisms of action remain unclear. Previous studies have implicated a wide range of molecular targets in cardiac muscle for the major green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), but effects were observed only at micromolar concentrations of unclear clinical relevance. Here, we report that nanomolar concentrations of EGCG significantly enhance contractility of intact murine myocytes by increasing electrically evoked Ca2+ transients, sarcoplasmic reticulum (SR) Ca2+ content, and ryanodine receptor type 2 (RyR2) channel open probability. Voltageclamp experiments demonstrate that 10 nM EGCG significantly inhibits the Na +-Ca2+ exchanger. Of importance, other Na+ and Ca2+ handling proteins such as Ca2+-ATPase, Na +-H+ exchanger, and Na+-K+-ATPase were not affected by EGCG ≤1 μM. Thus, nanomolar EGCG increases contractility in intact myocytes by coordinately modulating SR Ca2+ loading, RyR2- mediated Ca2+ release, and Na+-Ca 2+ exchange. Inhibition of Na+-K+-ATPase activity probably contributes to the positive inotropic effects observed at EGCG concentrations >1 μM. These newly recognized actions of nanomolar and micromolar EGCG should be considered when the therapeutic and toxicological potential of green tea supplementation is evaluated and may provide a novel therapeutic strategy for improving contractile function in heart failure.

Original languageEnglish (US)
Pages (from-to)993-1000
Number of pages8
JournalMolecular Pharmacology
Volume82
Issue number5
DOIs
StatePublished - Nov 2012

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Catechin
Tea
Cardiac Myocytes
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum
Muscle Cells
Literature
Sodium-Hydrogen Antiporter
Calcium-Transporting ATPases
epigallocatechin gallate
Toxicology
Myocardium
Therapeutics
Heart Failure
Health

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Feng, W., Hwang, H. S., Kryshtal, D. O., Yang, T., Padilla, I. T., Tiwary, A. K., ... Knollmann, B. C. (2012). Coordinated regulation of murine cardiomyocyte contractility by nanomolar (-)-epigallocatechin-3-gallate, the major green tea catechin. Molecular Pharmacology, 82(5), 993-1000. https://doi.org/10.1124/mol.112.079707

Coordinated regulation of murine cardiomyocyte contractility by nanomolar (-)-epigallocatechin-3-gallate, the major green tea catechin. / Feng, Wei; Hwang, Hyun Seok; Kryshtal, Dmytro O.; Yang, Tao; Padilla, Isela T.; Tiwary, Asheesh K.; Puschner, Birgit; Pessah, Isaac N; Knollmann, Björn C.

In: Molecular Pharmacology, Vol. 82, No. 5, 11.2012, p. 993-1000.

Research output: Contribution to journalArticle

Feng, Wei ; Hwang, Hyun Seok ; Kryshtal, Dmytro O. ; Yang, Tao ; Padilla, Isela T. ; Tiwary, Asheesh K. ; Puschner, Birgit ; Pessah, Isaac N ; Knollmann, Björn C. / Coordinated regulation of murine cardiomyocyte contractility by nanomolar (-)-epigallocatechin-3-gallate, the major green tea catechin. In: Molecular Pharmacology. 2012 ; Vol. 82, No. 5. pp. 993-1000.
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