Funding Source: American Heart Association AIREA (Academic Institution Research Enhancement Award) 23AIREA1051613 – We study two proteins, hERG and KvLQT1, found in heart muscle cells. These two proteins form ion channels, tunnels through the cell membrane that allow ions to move into or out of the cell in a selective and controlled way. The movement and balance of ions set the pace of a normal human heartbeat. When the pace is disrupted, people can experience irregular heartbeats, heart damage, or sudden cardiac death. We think that hERG and KvLQT1 function less well when they are connected or bound to each other. This could increase the chance of irregular heartbeats. Thus we are interested in what cellular signals tell hERG and KvLQT1 to bind or to release. We have shown that the final signal step in the “fight or flight” response of organisms chemically alters hERG and KvLQT1 proteins. This chemical change seems to cause the two proteins to release each other. In this proposal we will study the multiple places where this chemical change can happen in both hERG and KvLQT1. We think we will see different levels of binding depending on the extent and location each protein is altered. We will also study whether these chemical changes cause more or less hERG and KvLQT1 to be present in the cell membrane. An increase in protein amount in the cell membrane would allow more ions to flow, helping maintain a normal heartbeat. Overall our work may connect protein-protein interactions to the rhythmic functioning or malfunctioning of human hearts.