Mitochondrial Buffering of Calcium in the Heart

Abstract

See related article, pages 172–182 The kinetics of mitochondrial Ca2+ cycling and its precise role in controlling local Ca2+ fluxes in intact cardiac myocytes has not been fully elucidated. In the case of cardiac excitation–contraction (E-C) coupling in normal cardiac atrial cells, it has been established that cytosolic Ca2+ ([Ca2+]c) increases peripherally within the cell and propagates to the center.1 What is less clear has been the understanding of the time scale dynamics of the Ca2+ fluxes within the mitochondria. To began to address whether beat-to-beat changes in [Ca2+]c alter mitochondrial Ca2+ loading, Maack and colleagues2 use a novel technique to monitor, simultaneously, Ca2+ concentrations in the cytoplasm and mitochondrial matrix. Additionally, the authors’ probe the effect that mitochondrial Ca2+ efflux, due to elevated Na+, could have on mitochondrial Ca2+ buffering and bioenergetics. It is well recognized that the energetic cost of mechanical/contractile work plus ion handling associated with E-C coupling is very high and is supported by the large mitochondrial volume fraction of the cardiac myocyte. The link between regulation of ATP production and intracellular calcium fluxes has been suggested by studies that have demonstrated that the transport of Ca2+ into the mitochondrial matrix can activate several enzymes of the TCA cycle. It is well-known that mitochondria sequester Ca2+ ([Ca2+]m) under conditions that increase [Ca2+]c concentrations in many different cell types.3–5 Changes in [Ca2+]m can have effects on energy production rates, amplitude, and temporal profiles of [Ca2+]c as well as its well …