Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure

A. M. Gómez, H. H. Valdivia, H. Cheng, Miriam R. Lederer, Luis Fernando Santana, M. B. Cannell, S. A. McCune, R. A. Altschuld, W. J. Lederer

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608 Scopus citations

Abstract

Cardiac hypertrophy and heart failure caused by high blood pressure were studied in single myocytes from hypertensive rats (Dahl SS/Jr) and SH-HF rats in heart failure. Confocal microscopy and patch-clamp methods were used to examine excitation-contraction (EC) coupling, and the relation between the plasma membrane calcium current I(Ca) and evoked calcium release from the sarcoplasmic reticulum (SR), which was visualized as 'calcium sparks.' The ability of I(Ca) to trigger calcium release from the SR in both hypertrophied and failing hearts was reduced. Because i(Ca) density and SR calcium-release channels were normal, the defect appears to reside in a channels in the relation between SR calcium-release channels and sarcolemmal calcium channels. β-Adrenergic stimulation largely overcome the defect in hypertrophic but not failing heart cells. Thus, the same defect in EC coupling that develops during hypertrophy may contribute to heart failure when compensatory mechanisms fail.

Original languageEnglish (US)
Pages (from-to)800-806
Number of pages7
JournalScience
Volume276
Issue number5313
DOIs
StatePublished - May 2 1997
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)
  • General

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    Gómez, A. M., Valdivia, H. H., Cheng, H., Lederer, M. R., Santana, L. F., Cannell, M. B., McCune, S. A., Altschuld, R. A., & Lederer, W. J. (1997). Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure. Science, 276(5313), 800-806. https://doi.org/10.1126/science.276.5313.800