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

Caption: Isolated rat heart cell- the proteins involved with lactic acid transport across the plasma membrane labelled with fluorescent antibodies and visualized with confocal microscopy (Data from Prof Halestrap’s laboratory)

Where

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

How ‌

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

  • Confocal Imaging
  • Electron microscopy
  • Measurements of contractile activity (cells and hearts)
  • Electrophysiological recording (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 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

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 
  • The cardiac sarcoplasmic reticulum in health and disease‌
  • 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

More information

Further details on research in cardiac physiology and mitochondrial function can be found by visiting pages of key researchers in this field. 

 

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