Regulation of mitochondrial ATP production and Ca 2+ signalling in cardiomyocytes
Aerobic energy production in the heart is essential for the maintenance of normal contractility, but the mechanisms through which ATP homeostasis is achieved are incompletely understood.
We are investigating control of ATP production in normal and diseased (ischaemic/reperfused) hearts, using single cardiomyocytes as a model. We are able to measure mitochondrial and cytosolic [Ca 2+] using fluorescent dyes or targeted proteins such as aequorin, and mitochondrial and cytosolic [ATP] using luciferase. We are also investigating whether mitochondrial Ca 2+-transport plays a role in excitation-contraction coupling, particularly whether mitochondrial Ca 2+ spikes occur on a beat-to-beat basis in the heart.
We are also using single-cell models of ischaemia reperfusion injury to investigate the role of Ca 2+ and reactive oxygen species (ROS) in cell injury under these conditions, in particular during ischaemic-preconditioning and during postnatal development of the heart.
Bell CJ, Bright N, Rutter GA, Griffiths EJ. (2006) ATP regulation in adult rat cardiomyocytes: Time resolved decoding of rapid mitochondrial calcium spiking imaged with targeted photoproteins. Journal of Biological Chemistry. 281(38):28058-28067.
Warraich RS, Griffiths EJ, Bell CJ, Suleiman M-S, Dunn MJ, Angelini GD, Falconar AK, Yacoub M-H. (2006) Human cardiac myosin autoantibodies impair myocyte contractility: a cause-and-effect relationship. FASEB Journal. 20(6):651-660.
Bell CJ, Rutter GA, Griffiths EJ. (2005) Mitochondrial and cytosolic calcium transients in adult cardiomyocytes detected using targeted aequorin. Journal of Physiology. 567P C96.
Suleiman MS, Halestrap, AP, Griffiths EG. (2001) Mitochondria: a target for myocardial protection. Pharmacology and Therapeutics. 89: 29-46.