Cardiac physiology and mitochondrial function

What

We are interested in the mechanisms that underlie the electrical activity, energy production, ion handling and contraction of the heart.

Our research investigates how these mechanisms function normally, and how they are altered in pathological conditions. These include the damage to the heart following a coronary thrombosis or heart surgery, and disease states and inherited conditions that lead to abnormal cardiac rhythms and failure of contraction.

The image above is of a single heart muscle cell - a myocyte - stained to show one of the proteins we study that is essential for energy metabolism.

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Where

Research is mainly conducted in the Schools of Biochemistry and of Physiology and Pharmacology in the Medical Sciences Building, and in the School of Clinical Sciences at the Bristol Royal Infirmary.

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How

Characteristic methods and techniques routinely used in this area of research include:

Confocal Imaging
Electron microscopy (image top right shows electrograph of a cardiac mitochondrion)
Measurements of contractile activity (cells and hearts)
Electrophysiological recording (individual channels in bilayers, from cells, multicellular preparations and hearts)
Immunohistochemistry
Real time measurement of ions, reactive oxygen species and mitochondrial function using fluorescent dyes in isolated mitochondria, cardiac myocytes (see top image) and the Langendorff perfused heart
Measurement of respiration in isolated cells and mitochondria with an oxygen electrode
Measurement of membrane transport phenomena using radioactive and fluorescent techniques
Mathematical modelling of electrical activity and ion handling
Molecular biology and protein chemistry
Molecular modelling of membrane proteins and drug interactions
Proteomics
Ion channel and transporter pharmacology

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Highlights

Current projects include:

The mechanism of the mitochondrial permeability transition and its role in reperfusion injury and cardioprotection.
The mechanism of lactate and pyruvate transport across the plasma and mitochondrial membranes (image shows cross section of a mitochondrion with its internal membranes)
The cardiac sarcoplasmic reticulum (SR) in health and disease - encompassing ryanodine receptors and novel SR ion channels.
Calcium handling and arrhythmias
Inherited and acquired arrhythmia syndromes
Excitation-contraction (EC) coupling, encompassing mechanisms of triggering and terminating calcium release events and subcellular localisation of channels and transporters in both normal and disease states.
Atrial fibrillation and atrial remodelling
The atrioventricular node of the cardiac pacemaker-conduction system