Diastolic calcium is elevated in metabolic recovery of cardiomyocytes expressing elevated levels of the Na+/H+ exchanger

I. Baczkó, Fatima Mraiche, Peter E. Light, Larry Fliegel

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In the myocardium, the Na+/H+ exchanger isoform 1 (NHE1) plays a pivotal role in mediating ischemia-reperfusion (I/R) injury by causing intracellular Na+ accumulation that results in a subsequent increase in intracellular calcium (Ca2+ overload). One of the major clinical correlates of I/R injury is contractile dysfunction, in which Ca 2+ overload via increased Na+/Ca2+ exchange is a major contributor. To better understand the cellular role of NHE1 during I/R injury, contractile function and calcium transients were measured during metabolic inhibition and recovery in single ventricular myocytes from transgenic mice with elevated NHE1 expression. During normoxic conditions, no differences were seen between NHE1-overexpressing cardiomyocytes and wild-type (WT) cardiomyocytes with respect to fractional cell shortening (FCS), rate of shortening (+dL/dt), and rate of relaxation (-dL/dt). When metabolic recovery followed metabolic inhibition, NHE1-overexpressing ventricular myocytes exhibited a significant increase in FCS (130.2% ± 11.77% baseline) and ±dL/dt (146.93% ± 12.27% baseline). This correlated with a significant increase in the concentration of diastolic intracellular calcium, which was attenuated by the NHE1 inhibitor HOE694. These results indicate that in normoxic conditions, elevated NHE1 expression does not alter contractile function. During metabolic recovery, however, elevated NHE1 expression increased diastolic Ca2+ loading that led to augmented cell contractility.

Original languageEnglish
Pages (from-to)850-859
Number of pages10
JournalCanadian Journal of Physiology and Pharmacology
Volume86
Issue number12
DOIs
Publication statusPublished - Dec 2008

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Sodium-Hydrogen Antiporter
Cardiac Myocytes
Protein Isoforms
Calcium
Reperfusion Injury
Muscle Cells
Transgenic Mice
Myocardium

Keywords

  • Ca transient
  • Contractile function
  • Heart failure
  • Metabolic inhibition
  • Metabolic recovery
  • Na/H exchanger

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

Cite this

Diastolic calcium is elevated in metabolic recovery of cardiomyocytes expressing elevated levels of the Na+/H+ exchanger. / Baczkó, I.; Mraiche, Fatima; Light, Peter E.; Fliegel, Larry.

In: Canadian Journal of Physiology and Pharmacology, Vol. 86, No. 12, 12.2008, p. 850-859.

Research output: Contribution to journalArticle

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