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Cardiac ischemia followed by reperfusion results in cardiac cell death, which has been attributed to an increase of mitochondrial Ca2+ concentration, resulting in activation of the mitochondrial permeability transition pore (PTP). Evaluating this hypothesis requires understanding of the mechanisms responsible for control of mitochondrial Ca2+ in physiological conditions and how they are altered during both ischemia and reperfusion. Ca2+ influx is thought to occur through the mitochondrial Ca2+ uniporter (MCU). However, with deletion of the MCU, an increase in mitochondrial Ca2+ still occurs, suggesting an alternative Ca2+ influx mechanism during ischemia. There is less certainty about the mechanisms responsible for Ca2+ efflux, with contributions from both Ca2+/H+ exchange and a Na+ -dependent Ca2+ efflux pathway. The molecular details of both mechanisms are not fully resolved. We discuss this and the contributions of both pathways to the accumulation of mitochondrial Ca2+ during ischemia and reperfusion. We further discuss the role of mitochondrial Ca2+ in activation of the PTP. [ABSTRACT FROM AUTHOR]

The Journal of Physiology published an Opinion article critiquing a study on calcium flux balance in cardiac myocytes. The article emphasizes the importance of maintaining calcium flux balance in the heart to prevent calcium overload and cell death. It discusses the role of various factors such as diastolic, systolic, and average calcium concentrations, as well as the control of sarcoplasmic reticulum calcium content. The study also addresses the effects of altering proteins involved in calcium handling and the implications of drugs that affect calcium release. [Extracted from the article]

The article in the Journal of Physiology provides a brief response to Terrar's comments on calcium flux and RyR. The authors acknowledge Terrar's observations on Ca2+ extrusion differences during voltage clamp pulses and action potentials. They also address criticisms regarding temperature variations in their experiments and discuss the complexities of Ca2+ extrusion via NCX during action potentials. The study was funded by the British Heart Foundation. [Extracted from the article]

A recent study published in the Proceedings of the National Academy of Sciences reveals that the concentration of adenosine triphosphate (ATP) in cells is much lower than previously believed. This has important implications for cellular functions, especially in the heart where ATP is crucial for contraction and pumping blood. The study used a new fluorescent sensor to measure ATP levels in single cells and found that ATP levels in the cytoplasm were around 500 μM during diastole, much lower than previous estimates. The study also suggests that low ATP levels may activate ATP-sensitive potassium channels, potentially protecting against arrhythmias. The article discusses the regulation of ATP during excitation-contraction coupling in ventricular myocytes and highlights the role of mitochondria in ATP production. It also emphasizes the importance of ATP in calcium binding and diffusion, as well as its impact on metabolism in the heart and other organs. [Extracted from the article]