Exploring Impaired SERCA Pump-Caused Alternation Occurrence in Ischemia

Impaired sarcoplasmic reticulum (SR) calcium transport ATPase (SERCA) gives rise to Ca²⁺ alternans and changes of the Ca2+release amount. These changes in Ca²⁺ release amount can reveal the mechanism underlying how the interaction between Ca²⁺ release and Ca²⁺ uptake induces Ca²⁺ alternans. This study of alternans by calculating the values of Ca²⁺ release properties with impaired SERCA has not been explored before. Here, we induced Ca²⁺ alternans by using an impaired SERCA pump under ischemic conditions. The results showed that the recruitment and refractoriness of the Ca²⁺ release increased as Ca²⁺ alternans occurred. This indicates triggering Ca waves. As the propagation of Ca waves is linked to the occurrence of Ca²⁺ alternans, the "threshold" for Ca waves reflects the key factor in Ca²⁺ alternans development, and it is still controversial nowadays. We proposed the ratio between the diastolic network SR (NSR) Ca content (Ca_nsr) and the cytoplasmic Ca content (Ca ) (Ca_nsr/Ca ) as the "threshold" of Ca waves and Ca²⁺ alternans. Diastolic Ca_nsr, Ca , and their ratio were recorded at the onset of Ca²⁺ alternans. Compared with certain Ca_nsr and Ca , the "threshold" of the ratio can better explain the comprehensive effects of the Ca²⁺ release and the Ca²⁺ uptake on Ca²⁺ alternans onset. In addition, these ratios are related with the function of SERCA pumps, which vary with different ischemic conditions. Thus, values of these ratios could be used to differentiate Ca²⁺ alternans from different ischemic cases. This agrees with some experimental results. Therefore, the certain value of diastolic Ca_nsr/Ca can be the better "threshold" for Ca waves and Ca²⁺ alternans.