Dr Sarah Hall - PhD
All behaviour is generated and controlled at the cellular level by electrical impulses which regulate muscle contraction and the secretion of hormones. The transmission of electrical signals between cells occurs via specific ion channel proteins, which provide a conduit for electrical currents across cell membranes. The opening and closing behaviour of ion channels can be monitored using patch-clamp recording techniques to measure current flow through individual channel proteins. Since these currents co-ordinate the functioning of cells, ion channel behaviour is tightly controlled and regulated by nervous and hormonal influences. Chemical modification (phosphorylation or dephosphorylation) of the channel proteins by enzymes inside the cell provides one important mechanism of ion channel regulation. Our research is focused on the modulation of ion channel activity in cardiac and neuroendocrine cells by intracellular signal transduction pathways mediating reversible protein phosphorylation.
Our research falls into two broad areas:
1. We are investigating electrophysiological events and intracellular signalling mechanisms associated with cell swelling and subsequent volume regulation in isolated cardiac cells. By identifying the cascade of events linking the initial swelling stimulus to the volume regulatory response, we may help to limit cardiac cell damage during myocardial ischaemia and reperfusion, and could prolong the viability of cardiac tissue during heart surgery and transplantation.
2. We are also studying the molecular mechanisms mediating regulation of calcium-activated, potassium-selective channels ('BK' channels) by reversible protein phosphorylation. BK channels play a fundamental role in the control of many cell functions, including electrical activity in nerves, development of blood vessel tone and secretion of hormones; moreover, abnormal regulation of BK channels has been implicated in disease states such as Alzheimer's disease and hypertension. Our work aims to determine which potential phosphorylation sites on BK channel proteins are crucial for regulation of ion channel behaviour. This work will advance our knowledge of how hormones and toxins can alter cell function by altering the phosphorylation state of ion channels.
Wellcome Trust, Physiological Society, Biochemical Society
Dr Jean Assender, Cardiff University and University of Birmingham
Dr Darrell Evans, Cardiff University and University of Brighton and Sussex
Dr David Armstrong, NIEHS, NIH