Reduced calcium current density in single myocytes isolatedfrom hypertrophied failing guinea pig hearts

Zhen Ming, Charles Nordin, Francis Siri, Ronald S. Aronson

Research output: Contribution to journalArticle

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Abstract

The present study explored the possibility that an alteration in the transmembrane calcium current (ICa), through its ability to modulate Ca2+ release from the sarcoplasmic reticulum, could contribute to the depressed peak [Ca2+]i we previously observed in hypertrophied failing myocardium. Whole-cell patch clamp was used to measure ICa in single guinea pig ventricular myocytes isolated from hearts of normal guinea pigs andfrom guinea pig hearts in which hypertrophy and failure were induced by gradually developing left ventricular pressure overload subsequent to ascending aortic banding of young animals. Membrane capacitance (Cm) was significantly greater, and ICa, normalized for Cm was significantly lower in myocytes from hypertrophied failing hearts. Myocytes from hypertrophied failing hearts did not differ significantly from normal myocytes in terms of the voltage-dependence of the activation variable (d) of ICa (except at − 30 mV), the time course of removal of inactivation of ICa, and the time constant of decay of ICa. Measurement of the voltage dependence of the inactivation variable (f) of ICa showed that significantly more steady-state inactivation was present at 0, −10, and −20 mV inmyocytes from hypertrophied failing hearts. Multiple regression analysis of all data indicated that ICa density decreased with increasing myocyte membrane area (as reflected by Cm) irrespective of any specific effects of hypertrophy and heart failure. We conclude that ICa, normalized for Cm, is significantly reduced in myocytes isolated from hypertrophiedfailing hearts, probably by a process associated with increased cell size, per se.

Original languageEnglish (US)
Pages (from-to)1133-1143
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume26
Issue number9
DOIs
Publication statusPublished - Sep 1994

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Keywords

  • Calcium current
  • Cardiac hypertrophy
  • Cardiac myocytes

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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