Role of slowed Ca2+ transient decline in slowed relaxation during myocardial ischemia

Jessica M. Halow, Vincent M. Figueredo, David M. Shames, S. Albert Camacho, Anthony J. Baker

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The goal of this study was to test the hypothesis that during myocardial ischemia, slowing of the Ca2+ transient decline causes slowed relaxation. Our approach was to monitor pressure and Ca2+ transients in isovolumic rat hearts during control and low flow ischemia conditions. In addition, we experimentally slowed the decline of the Ca2+ transient using cyclopiazonic acid (CPA) to inhibit the sarcoplasmic reticulum Ca2+-ATPase (SERCA, the most important pump for rapidly transporting Ca2+ out of the cytosol). Using 9 μM CPA during normoxia, we were able to reproduce the slowed Ca2+ transient decline and slowed relaxation found during low flow ischemia. The time constants of cytosolic [Ca2+] decline and pressure decline (τ(Ca) and τ(p) respectively) with CPA (78 ± 5 ms and 64 ± 3 ms) were similar to those found with ischemia (89 ± 12 ms and 72 ± 10 ms, mean ± SEM, n = 7) and were considerably greater than for controls (41 ± 3 and 25 ± 2 ms, mean ± SEM, n = 14, P < 0.01). Furthermore, the relationship of τ(p) v τ(Ca) with CPA was similar to that found with ischemia. These findings are consistent with the hypothesis that the slowed Ca2+ transient decline with both CPA and ischemia causes slowed relaxation. Consistent with this conclusion, a simple mathematical model to relate cytosolic [Ca2+] and pressure also suggests that slowed pressure relaxation can be explained by slowing of the Ca2+ transient decline. This study suggests that impaired Ca2+ uptake is a major injury causing slowed relaxation during ischemia.

Original languageEnglish (US)
Pages (from-to)1739-1748
Number of pages10
JournalJournal of molecular and cellular cardiology
Volume31
Issue number9
DOIs
StatePublished - Sep 1999
Externally publishedYes

Keywords

  • Calcium
  • Cyclopiazonic acid
  • Fluorescence
  • Indo-1
  • Isovolumic
  • Langendorff
  • Rat
  • SERCA

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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