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 Ca²⁺ 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 Ca²⁺-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 Ca²⁺-ATPase (SERCA2a), Na⁺/Ca²⁺ exchanger, mitochondrial Ca²⁺ uniporter, and ryanodine receptor contents. IR-induced damage to ryanodine receptor stimulates Ca²⁺ leakage in 6-month-old hearts and elevated phospholamban (PLN)-to-SERCA2a ratio can slow down Ca²⁺ reuptake seen at 2-5 μM Ca²⁺. Total and monomeric PLN mirrored the response of overexpressed SERCA2a after IR in 24-month-old hearts, resulting in stable Ca²⁺-ATPase activity. Upregulated PLN accelerated inhibition of Ca²⁺-ATPase activity at low free Ca²⁺ in 15-month-old after IR, and reduced SERCA2a content subsequently impairs the Ca²⁺-sequestering capacity. In conclusion, our study suggests that aging is associated with a significant decrease in the abundance and function of Ca²⁺-handling proteins. However, the IR-induced damage was not increased during aging.