Thermal injury alters myocardial sarcoplasmic reticulum calcium channel function

Joseph T. Murphy, Brett Giroir, Jureta W. Horton

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background. We have previously shown that a major cutaneous thermal injury produces profound cardiac contractile dysfunction despite adequate resuscitation. While the molecular basis of this dysfunction is unknown, recent work has suggested that alterations in calcium flux between the myocyte sarcoplasmic reticulum (SR) to the cytoplasm may play a role. Materials and methods. To determine if thermal injury-induced contractile dysfunction is related to intracellular calcium transport across the SR membrane, we accessed myocardial microsomal preparations from scalded (43% TBSA) guinea pigs for the ability of the cardiac calcium efflux channel to bind radiolabeled ryanodine. Intracellular calcium flux was assessed by fluorescence spectrophotometry. Results. Thermal injury resulted in severe cardiac contractile deficit characterized by loss of LVP and ±dP/dt despite resuscitation. Analysis of isolated myocyte cultures showed a twofold increase in cytoplasmic [Ca2+]1 by 24 h postburn. Competitive binding and scatchard analysis demonstrated a single, high-affinity binding site present in both sham and burn animal hearts. Myocardial membrane vesicles revealed a significantly enhanced number of calcium efflux channels in the open configuration at both 8 and 24 h following thermal injury compared to time- matched shams (1.07 ± 0.01 and 0.95 ± 0.06 vs 0.85 ± 0.01 pmol bound/mg protein, P < 0.05). The data indicate that altered function of the myocardial transmembrane SR calcium efflux channel following thermal injury was associated with elevated [Ca2+]1 and contractile dysfunction. Conclusions. We conclude that postburn cardiac dysfunction may partly be a result of elevated cytoplasmic calcium concentrations and diminished regulation of SR calcium efflux channel activity.

Original languageEnglish (US)
Pages (from-to)244-252
Number of pages9
JournalJournal of Surgical Research
Volume82
Issue number2
DOIs
StatePublished - Apr 1999

Keywords

  • Cardiac dysfunction
  • Intracellular calcium
  • Ryanodine receptor
  • Thermal injury

ASJC Scopus subject areas

  • Surgery

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