Is Na/Ca exchange during ischemia and reperfusion beneficial or detrimental?
Cytosolic calcium increases to approximately 3 micro M after 15 min of global ischemia. Manipulations that attenuate this increase in cytosolic Ca(2+) reduce myocyte death and dysfunction. The increase in cytosolic Ca(2+) during ischemia is dependent on an increase in intracellular Na(+), suggesting a role for Na/Ca exchange. Typical ischemic values for ionized intra- and extracellular Na(+), Ca(2+), and membrane potential are consistent with the Na/Ca exchanger operating near equilibrium during ischemia. Studies were undertaken using hearts from mice that overexpress the Na/Ca exchanger to determine if Na/Ca exchanger overexpression enhances or reduces ischemic injury. These studies suggest that overexpression of the Na/Ca exchanger enhances injury in males, but females are protected by a gender-related mechanism.
Murphy
Elizabeth
E
Laboratory of Signal Transduction, National Institute for Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. murphy1@niehs.nih.gov
Cross
Heather R
HR
Steenbergen
Charles
C
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D007700:Kinetics; D008564:Membrane Potentials; D015424:Reperfusion; D015427:Reperfusion Injury / Q000503:physiopathology*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium