Figure 9. A putative model of the local interactions between mitochondrial Ca²⁺ uniporter (MCU), mitochondrial Na⁺–Ca²⁺ exchanger (MNCE) and endoplasmic reticulum inositol 1,4,5-trisphosphate receptor (InsP₃R).

Ca²⁺ released through InsP₃R is rapidly transported into mitochondria via MCU and then extruded from this organelle through MNCE. 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) activates MCU and CGP37157 inhibits MNCE, so in the presence of both drugs, Ca²⁺ is accumulated into mitochondria thus reducing the size of the local cytosolic [Ca²⁺] microdomain around InsP₃R. The plasma membrane (PMCA) and endoplasmic reticulum (ER) Ca²⁺ pumps (SERCA) restore cytosolic and ER [Ca²⁺] to resting levels in the intervals between oscillations. For this, Ca²⁺ entry through store-operated channels (SOCs) is also essential. ERM, ER membrane; MOM, mitochondrial outer membrane; MIM, mitochondrial inner membrane; PM plasma membrane.