Effect of long-term heat strain on calcium signaling in the murine myocardium

The physiological effects of prolonged heat strain (HS) insufficient to cause heat stroke on the heart remain poorly understood. We previously established that this causes cellular injury and stress in the murine heart. Given that calcium dysregulation can lead to these previously detected changes, the purpose of this investigation was to determine the extent to which HS altered calcium homeostasis in the murine myocardium. We hypothesized that HS would undermine calcium homeostatic control. To test this hypothesis, 7-wk-old female mice were assigned to either thermoneutral (TN; <i>n</i> = 8, 31.2 ± 1.0°C, 35 ± 1% humidity) or HS (<i>n</i> = 9; 37.6 ± 0.0°C, 42 ± 1% humidity) conditions for 24 h. In comparison with TN, HS increased protein abundance of plasma membrane calcium ATPase by 19% (<i>P</i> = 0.05), phosphorylated (p)-phospholamban by 426% (<i>P</i> < 0.01), calmodulin-dependent protein kinase II by 142% (<i>P</i> < 0.01), CaM by 37% (<i>P</i> < 0.01), and calsequestrin by 58% (<i>P</i> < 0.05); however, HS decreased phopholamban by 25% (<i>P</i> = 0.05) and p-protein kinase A by 58% (<i>P</i> < 0.01) compared with TN. These data demonstrate that 24 h of subheat stroke HS is sufficient to induce calcium signaling protein changes in the myocardium that favor calcium clearance from the cytosol into the SR with concomitant desensitization to β-adrenergic stimulation. However, how calcium dysregulation may lead to functional impairments is unknown.<b>NEW & NOTEWORTHY</b> Prolonged environmental heat exposure threatens cardiovascular health, yet underlying mechanisms remain poorly defined. Here, we show that 24 h of heat strain altered cardiac calcium handling. Heat strain appeared to increase cytosolic calcium clearance via a CaMKII/CaM/phospholamban-mediated activation of sarco(endo)plasmic reticulum calcium (SERCA) and subsequent SR sequestration. Interestingly, decreased PKA phosphorylation may be suggestive of blunted β-adrenergic stimulation. These findings implicate calcium dysregulation as a key contributor to myocardial stress during sustained heat exposure.