Exploring impaired SERCA pump-caused alternation occurrence in ischemia (Q2283789)

Summary: Impaired sarcoplasmic reticulum (SR) calcium transport ATPase (SERCA) gives rise to Ca\(^{2+}\) alternans and changes of the Ca\(^{2+}\) release amount. These changes in Ca\(^{2+}\) release amount can reveal the mechanism underlying how the interaction between Ca\(^{2+}\) release and Ca\(^{2+}\) uptake induces Ca\(^{2+}\) alternans. This study of alternans by calculating the values of Ca\(^{2+}\) release properties with impaired SERCA has not been explored before. Here, we induced Ca\(^{2+}\) alternans by using an impaired SERCA pump under ischemic conditions. The results showed that the recruitment and refractoriness of the Ca\(^{2+}\) release increased as Ca\(^{2+}\) alternans occurred. This indicates triggering Ca waves. As the propagation of Ca waves is linked to the occurrence of Ca\(^{2+}\) alternans, the ``threshold'' for Ca waves reflects the key factor in Ca\(^{2+}\) alternans development, and it is still controversial nowadays. We proposed the ratio between the diastolic network SR (NSR) Ca content (Ca\(_{\mathrm{nsr}})\) and the cytoplasmic Ca content (Ca\(_i\)) (Ca\(_{\mathrm{nsr}}\)/Ca\(_i\)) as the ``threshold'' of Ca waves and Ca\(^{2+}\) alternans. Diastolic Ca\(_{\mathrm{nsr}}\), Ca\(_i\), and their ratio were recorded at the onset of Ca\(^{2+}\) alternans. Compared with certain Ca\(_{\mathrm{nsr}}\) and Ca\(_i\), the ``threshold'' of the ratio can better explain the comprehensive effects of the Ca\(^{2+}\) release and the Ca\(^{2+}\) uptake on \(Ca^{2+}\) 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 Ca\(^{2+}\) alternans from different ischemic cases. This agrees with some experimental results. Therefore, the certain value of diastolic Ca\(_{\mathrm{nsr}}\)/Ca\(_i\) can be the better ``threshold'' for Ca waves and Ca\(^{2+}\) alternans.