Pumping out sodium to restore heart function in heart failure

Regulation of the cardiac Na/K ATPase in health and disease

To work normally, heart muscle cells need to turn precise electrical impulses from nerves into the contracting motion of the heartbeat. During the heartbeat, each muscle cell releases a minutely timed burst of charged molecules to instruct its neighbours to pull together. After release, each cell gathers up these signalling molecules again and lets them out seconds later for the next beat. Mistakes in this tightly regulated process lead to diseases including heart failure. Professor Mike Shattock is a leading expert in one of the channel proteins on the outer cell membrane – the sodium pump. This ‘gatekeeper’ pumps sodium out of the cell and potassium in, maintaining the correct electrical difference between inside and outside the cell and allowing other signals to be passed over the membrane. Professor Shattock is focussing in particular on its role in heart failure where a build-up in sodium inside heart cells is well-known. Professor Shattock’s team has previously shown that defects in this channel protein contribute to this sodium build-up. Now the team aims to find a new drug to stimulate the channel, to better drive sodium out of the cells. More specifically, Professor Shattock aims to clarify how loss of sodium control in hypertrophy (an overgrowth of the heart) can lead to heart failure. One clue seems to lie in the malfunctioning of a particular part of the sodium pump, called phospholemman, which helps regulate how hard the sodium pump works. This project will lead to greater understanding of the processes occurring during heart failure, and could also lead to a new drug to relieve symptoms in patients.