How is the pH inside heart cells linked to heart disease?

Regulation of nuclear pH in ventricular myocytes and its role in gene expression

Dr Pawel Swietach and his colleagues at the University of Oxford are working out how pH influences gene activity within heart cells, and what happens in heart disease. Within healthy limits, changes in pH (how acidic or alkaline it is) can help to regulate the heart’s activities. However, extremes of pH are damaging, so we need to understand how heart cells regulate their pH. Dr Swietach has discovered that the cell ‘hub’ within heart cells, known as the nucleus, can regulate its own pH. Stress conditions inside cells, which can lead to heart conditions such as heart failure, change the pH of the nucleus. These changes in pH may have important effects on the genes. This is because genes are stored in the nucleus, and are ‘read’ differently as pH is changed. In this project, Dr Swietach will explore the molecules and processes that control the pH of the nucleus in heart cells and describe how they change in disease. He believes that substances called histidyl dipeptides may be particularly important in controlling the pH inside the nucleus of heart cells. By describing the control of pH in the nucleus and its effect on genes, Dr Swietach and his team could identify new targets for the treatment of heart disease.