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

Can J Physiol Pharmacol. 2008 Dec;86(12):850-9. doi: 10.1139/Y08-092.


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 Ca2+ 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cation Transport Proteins / antagonists & inhibitors
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Diastole / drug effects
  • Guanidines / pharmacology
  • Mice
  • Mice, Transgenic
  • Myocardial Contraction / drug effects
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / physiology
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers / antagonists & inhibitors
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / metabolism*
  • Stress, Physiological / drug effects
  • Stress, Physiological / physiology
  • Sulfones / pharmacology


  • Cation Transport Proteins
  • Guanidines
  • Slc9a1 protein, mouse
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers
  • Sulfones
  • 3-methylsulfonyl-4-piperidinobenzoyl guanidine
  • Calcium