How does the nano-location of molecules in cells impact the heartbeat in heart failure?

Function follows form: improving the failing heart by targeting signalling nanodomains in myocytes.

Our heartbeat is under the control of molecular signalling systems in each heart muscle cell. In diseases including heart failure these systems can break down, sending the heartbeat into irregular and sometimes fatal patterns. Researchers around the world are on a quest to understand why the heartbeat goes wrong and how to stop it from happening. Within heart muscle cells, tiny molecules that are involved in the heartbeat signalling system group together in particular areas, known as ‘nanodomains’. In the cells of failing hearts these molecules lose their proper grouping, location, and function. Using intricate techniques and high-resolution imaging of living cells, Professor Gorelik and her team will examine how the loss of signalling nanodomains leads to disruption of the heartbeat. The studies will take place in rats and in donated hearts from people with heart failure who have received a transplant. Healthy human hearts – donated but unused by the transplant service – will be studied for comparison. As well as examining the functions of protein nanodomain distribution and what happens to these domains in heart failure, the team will attempt to restore normal nanodomains with various chemical agents. If these are successful they could progress to become candidates for new heart failure medicines.