Regulation of intramitochondrial free calcium ([Ca2+]m) is critical in both physiological and pathological functioning of the heart. The full extent and importance of the role of [Ca2+]m is becoming apparent as evidenced by the increasing interest and work in this area of the last two decades. However, controversies remain, such as the existence of beat-to-beat mitochondrial Ca2+ transients; the role of [Ca2+]m in modulating whole-cell Ca2+ signalling; whether or not an increase in [Ca2+]m is essential to couple ATP supply and demand; and the role of [Ca2+]m in cell death by both necrosis and apoptosis, especially in formation of the mitochondrial permeability transition pore. The role of [Ca2+]m in heart failure is an area that has also recently been highlighted. [Ca2+]m can now be measured reasonably specifically in intact cells and hearts thanks to developments in fluorescent indicators and targeted proteins and more sensitive imaging technology. This has revealed interactions of the mitochondrial Ca2+ transporters with those of the sarcolemma and sarcoplasmic reticulum, and has gone a long way to bringing the mitochondrial Ca2+ transporters to the forefront of cardiac research. Mitochondrial Ca2+ uptake occurs via the ruthenium red sensitive Ca2+ uniporter (mCU), and efflux via an Na+/Ca2+ exchanger (mNCX). The purification and cloning of the transporters, and development of more specific inhibitors, would produce a step-change in our understanding of the role of these apparently critical but still elusive proteins. In this article I will summarise the key physiological roles of [Ca2+]m in ATP production and cell Ca2+ signalling in both adult and neonatal hearts, as well as highlighting some of the controversies in these areas. I will also briefly discuss recent ideas on interactions of nitric oxide with [Ca2+]m.
|Translated title of the contribution
|The ups and downs of mitochondrial calcium signalling in the heart
|856 - 864
|Number of pages
|Biochimica et Biophysica Acta (BBA) - Bioenergetics
|Published - Jun 2010