Age-Dependent Changes in Calcium Regulation after Myocardial Ischemia–Reperfusion Injury

During aging, heart structure and function gradually deteriorate, which subsequently increases susceptibility to ischemia–reperfusion (IR). Maintenance of Ca(2+) homeostasis is critical for cardiac contractility. We used Langendorff’s model to monitor the susceptibility of aging (6-, 15-, and 24-month-old) hearts to IR, with a specific focus on Ca(2+)-handling proteins. IR, but not aging itself, triggered left ventricular changes when the maximum rate of pressure development decreased in 24-month-olds, and the maximum rate of relaxation was most affected in 6-month-old hearts. Aging caused a deprivation of Ca(2+)-ATPase (SERCA2a), Na(+)/Ca(2+) exchanger, mitochondrial Ca(2+) uniporter, and ryanodine receptor contents. IR-induced damage to ryanodine receptor stimulates Ca(2+) leakage in 6-month-old hearts and elevated phospholamban (PLN)-to-SERCA2a ratio can slow down Ca(2+) reuptake seen at 2–5 μM Ca(2+). Total and monomeric PLN mirrored the response of overexpressed SERCA2a after IR in 24-month-old hearts, resulting in stable Ca(2+)-ATPase activity. Upregulated PLN accelerated inhibition of Ca(2+)-ATPase activity at low free Ca(2+) in 15-month-old after IR, and reduced SERCA2a content subsequently impairs the Ca(2+)-sequestering capacity. In conclusion, our study suggests that aging is associated with a significant decrease in the abundance and function of Ca(2+)-handling proteins. However, the IR-induced damage was not increased during aging.