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Novel stimulatory actions of the phytoestrogen genistein: effects on the gain of cardiac excitation‐contraction coupling
Author(s) -
Liew Reginald,
MacLeod Kenneth T.,
Collins Peter
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0760fje
Subject(s) - genistein , medicine , endocrinology , myocyte , contractility , chemistry , myofilament , endoplasmic reticulum , protein tyrosine phosphatase , biophysics , phosphorylation , biology , biochemistry
Genistein, a phytoestrogen found abundantly in soy products, is thought to be cardioprotective, partly through its ability to act as a natural Ca 2+ channel antagonist. However, the precise nature and significance of such direct cardiac actions remain obscure. We investigated the hypothesis that genistein exerts important additional actions on cardiac excitation‐contraction coupling (ECC). Genistein acutely increased cell shortening and the Ca 2+ transient in field stimulated guinea‐pig ventricular myocytes despite potently inhibiting the L‐type Ca 2+ current, I Ca,L . The specific phosphotyrosine phosphatase inhibitor, bpV(phen), diminished the stimulatory effects of genistein on myocyte contractility, suggesting that the mechanism partly involved tyrosine kinase inhibition. Genistein increased sarcoplasmic reticulum (SR) Ca 2+ load as measured with a caffeine pulse in Na + ‐free/ Ca 2+ ‐free solution. Furthermore, in the continued presence of caffeine, genistein increased the time constant of decline of the caffeine‐induced Ca 2+ transient, implying impaired sarcolemmal Na + /Ca 2+ exchanger function. Tetanization studies in intact myocytes revealed that 43% of cells exhibited increased myofilament Ca 2+ sensitivity in the presence of genistein. These findings demonstrate novel cardiac actions of genistein on the SR Ca 2+ load, Na + /Ca 2+ exchanger, and myofilament Ca 2+ sensitivity, which result in an overall increase in myocyte contractility and consequently the gain of ECC.