Studying the control of NCX1, a potential culprit in heart failure

The role of NCX1 palmitoylation in cardiac function

To pump blood around the body our heart must contract powerfully, before relaxing to allow it to refill once more. This process involves the synchronised ‘squeeze and release’ of every single heart muscle cell. When this tightly controlled process goes wrong, dangerous irregular heart rhythms can develop. Contraction and relaxation of individual heart cells depends on the movement of calcium ions in and out of the cell. When calcium leaves the cell, it relaxes. NCX1 is a protein that provides a route for calcium exit. Faults in NCX1 are associated with several heart and circulatory diseases, including heart failure. Dr Fuller and his team have discovered that NCX1 needs a temporary chemical modification - called palmitoylation – before it can let calcium exit the cell. In this study they will investigate exactly how this chemical change to NCX1 is regulated in heart cells, and what happens when it goes wrong. The team hopes to uncover parts of the NCX1 control system that could be drug targets. Future medicines aimed at NCX1 or its regulators may be able to safeguard the heart rhythm in people with heart failure and other cardiac conditions.