Cardiovascular Function Unit Laboratory 

Current research in The Cellular Biophysics Laboratory is aimed at understanding and developing better treatments for cardiac diseases. Our interests center on the mechanisms of arrhythmia (disturbances of heart rhythm which can range from uncomfortable to fatal) and hypertrophy. There are currently 3 postdoctoral fellows and 5 PhD students attached to the laboratory. There are several projects underway at present in the laboratory. Our major interest is in the response of the heart muscle to stretch and also how this is altered in certain disease states. Recently, it has become apparent that mechanical forces on the heart muscle, like stretch, can produce electrical changes in the muscle cells. These can be big enough to produce disturbances of heart rhythm. We hypothesise that these effects may underlie human arrhythmias such as atrial fibrillation and sudden cardiac death. We use a variety of techniques to study these arrhythmias, ranging through molecular biology, patch clamp, confocal microscopy, isolated heart studies and animal studies, and we have several collaborative projects investigating human cardiovascular diseases using techniques such as heart rate variability measures, measures of arterial stiffness and vascular reactivity.

For example, we use patch clamp recording of single ion channels in cardiac cells to show that a potassium channel sensitive to membrane stretch is present in the membrane of the cells. Molecular biology techniques are used to investigate the gene expression levels of this ion channel in human and animal hearts, and we are attempting to correlate the pattern of gene expression with the degree of stretch that different parts of the heart experience. We then use this information in experiments on isolated animal hearts to investigate the electrical and contractile responses to stretch, and to see if drugs that block the channel in the patch clamp experiments can stop the arrhythmias in the isolated hearts. We also investigate how the gene expression of the channels changes in diseases such as cardiac hypertrophy, to see if this can increase our understanding of these diseases.

We have recently shown that drugs which block a certain type of stretch sensitive ion channel are effective in stopping atrial fibrillation in rabbit hearts, which has profound implications for understanding the mechanism of atrial fibrillation in humans. We have also shown that the gene coding for a stretch sensitive potassium channel is expressed in human heart tissue. This may provide a new therapeutic target for the treatment of some cardiac diseases.

Since it is known that a Western diet (ie high fat) is a risk factor for cardiac death, we are also conducting studies to see if dietary interventions in animals can change the properties of the cardiac cells and alter the response to stretch of the heart. Similar studies are also being conducted in humans, to investigate whether dietary intervention can change the elasticity and reactivity of blood vessels.