Grant: Operating Grant

The object of our study is to examine the control of the activity of the Na+/H+ exchanger protein, that removes acid from inside the heart. Handling acid is a problem in all organisms. These 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 contract - that is the heart cannot pump blood well if there is excess acid inside the cells of the heart. In certain conditions such as ischemic heart disease, acid builds up, and this causes an inhibition of the heart's ability to contract and pump blood. We are studying the mechanism that deals with acid removal from inside heart cells and how it is regulated. There is a protein called the sodium proton exchanger (Na+/H+ exchanger) and its function is to remove the excess acid from inside the cells of the heart and take it out of the cells. In so doing, this protein brings in excess sodium into the heart. During heart disease, this results in an accumulation of intracellular sodium and this results in excess intracellular calcium through the actions of a sodium calcium exchanger protein. This exacerbates the problems that occur in ischemic heart disease and results in cell death and damage. We are studying how the protein is regulated in the heart which will give us insights into why its excess activity damages the heart.