Altered subcellular Ca2+ regulation in papillary muscles from cardiomyopathic hamster hearts

Am J Physiol. 1995 May;268(5 Pt 2):H1875-83. doi: 10.1152/ajpheart.1995.268.5.H1875.

Abstract

To investigate whether cardiac dysfunction in prefailure cardiomyopathic (CM) hamster hearts is due to Ca2+ overload or alternatively to decreased availability of Ca2+ in the sarcoplasmic reticulum (SR), the Ca2+ channel agonist, BAY K 8644, was used to compare the effects of increased Ca2+ influx on function and subcellular Ca2+ distribution in papillary muscles from hearts of 110-day-old CM and normal hamsters. A band, mitochondrial, and junctional SR Ca2+ were measured by electron probe microanalysis in CM and normal papillary muscles, which were either untreated or pretreated with BAY K 8644. Muscles were then rapidly frozen during contraction or relaxation. The results showed decreased tension development and decreased inotropic response to BAY K 8644 in CM muscles versus normals. There was no elevation of mitochondrial or A-band Ca2+ in BAY K 8644-treated or untreated CM muscles frozen during contraction or relaxation compared with similarly treated normals. In muscles frozen during relaxation, junctional SR Ca2+ was lower in both untreated and BAY K 8644-treated CM muscles versus comparably treated normals. These results do not support the hypothesis of an increased sensitivity to Ca2+ in hypertrophied, prefailure CM hearts but do indicate that less Ca2+ is available in the SR for activation of contraction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Calcium / metabolism*
  • Cardiomyopathies / metabolism*
  • Cardiomyopathies / physiopathology
  • Cricetinae
  • Electron Probe Microanalysis
  • In Vitro Techniques
  • Male
  • Mitochondria, Heart / metabolism
  • Myocardial Contraction
  • Myocardium / metabolism*
  • Papillary Muscles / metabolism*
  • Papillary Muscles / physiopathology
  • Sarcoplasmic Reticulum / metabolism
  • Subcellular Fractions / metabolism*

Substances

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Calcium