Mitochondrial Ca²⁺ uptake contributes to buffering cytoplasmic Ca²⁺ peaks in cardiomyocytes
2012
Drago, Ilaria | De Stefani, Diego | Rizzuto, Rosario | Pozzan, Tullio
Mitochondrial ability of shaping Ca ²⁺ signals has been demonstrated in a large number of cell types, but it is still debated in heart cells. Here, we take advantage of the molecular identification of the mitochondrial Ca ²⁺ uniporter (MCU) and of unique targeted Ca ²⁺ probes to directly address this issue. We demonstrate that, during spontaneous Ca ²⁺ pacing, Ca ²⁺ peaks on the outer mitochondrial membrane (OMM) are much greater than in the cytoplasm because of a large number of Ca ²⁺ hot spots generated on the OMM surface. Cytoplasmic Ca ²⁺ peaks are reduced or enhanced by MCU overexpression and siRNA silencing, respectively; the opposite occurs within the mitochondrial matrix. Accordingly, the extent of contraction is reduced by overexpression of MCU and augmented by its down-regulation. Modulation of MCU levels does not affect the ATP content of the cardiomyocytes. Thus, in neonatal cardiac myocytes, mitochondria significantly contribute to buffering the amplitude of systolic Ca ²⁺ rises.
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