Research groups

Research

Neonatal cardiomyocytes loaded with rhodamine 123 to measure mitochondrial membrane potential (A) healthy cells (B) cell treated with a mitochondrial uncoupler

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.

Recent publications

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. J Biol Chem 281(38):28058-67.

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 J. 20(6):651-60.

Bell CJ, Rutter GA & Griffiths EJ (2005).   Mitochondrial and cytosolic calcium transients in adult cardiomyocytes detected using targeted aequorin. J Physiol 567P C96.

Suleiman, M.S., Halestrap, A.P. and Griffiths, EG. ( 2001) Mitochondria: a target for myocardial protection. Pharmacology and Therapeutics 89 29-46.