Understanding how calcium pores open and close when the heart beats

Palmitoylation of the L-type Ca channel pore-forming subunit

When the heart beats, it’s essential that all heart muscle cells contract at the same time. To achieve this, tiny pores in the heart cells open simultaneously to allow calcium molecules to pass through, which in turn signal to the heart cells to beat. One of the ways that calcium pores are controlled is a process called palmitoylation, where a fat molecule is added to a protein molecule. Dr Fuller has found that a calcium pore called LTCC is ‘palmitoylated’ in heart muscle cells, and that this process is altered in heart failure. In this project, they will study the palmitoylation of LTCC in more detail to understand how it affects calcium movement. First, they plan to identify the enzymes that add and remove fat molecules from LTCC. This will allow them to alter the levels of these enzymes in heart muscle cells isolated from rabbits to study their effects. In addition to looking at the shape and function of the cells, they will study how removing these enzymes affects calcium movement and electrical currents – which are essential for the heart to beat normally. This research will increase our understanding of how calcium pores work, which could lead to the development of new ways to treat heart disease in the future.