Grant: Operating Grant

Ischemic heart disease and heart hypertrophy remain as key health problems debilitating or killing thousands of Canadians every year. We are studying a protein of the heart involved in both these pathologies, the Na+/H+ exchanger isoform 1 (NHE1). The Na+/H+ exchanger is a protein that removes acid from inside heart cells. The cells of the heart use food such as glucose and fat, to produce energy for the heart so that it can contract and pump blood. When this occurs, they produce waste products, and one of these is acid. Too much acid is bad for the heart. It inhibits the ability of the heart to pump blood. There is a protein called the Na+/H+ exchanger removes the excess acid from inside the cells of the heart. It turns out, that in ischemic heart disease and heart hypertrophy, the Na+/H+ exchanger activity is too activated and this tends to exacerbate these diseases. We are studying how this occurs. The Na+/H+ exchanger has a long intracellular tail. Proteins bind to the tail and this affects and regulates the activity of the Na+/H+ exchanger. We found that two proteins, calmodulin and B-Raf, bind to and regulate the Na+/H+ exchanger. We are characterizing how and when this occurs in the healthy and diseased heart. We are also investigating what other proteins bind to and regulate the Na+/H+ exchanger in the diseased heart. Our study will give novel insights into why Na+/H+ exchanger activity damages the heart and how this can be prevented.