Role of sodium permeability and pore structure in determining differences in the rates of voltage dependent opening and closing in hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels

The pacemaker cells of the heart are a small group of cells that beat spontaneously and set the beating frequency. On the surface of these cells are “pacemaker channels”, which open and close to allow potassium and sodium ions into the cells. The flow of these ions into the cell generates the spontaneous beating in the heart. The speed at which ions flow through the channels regulates how fast the pacemaker channel opens and closes, which in turn can affect heart rate. During exercise and stress, the amounts of these ions in the blood change and may affect the rate at which these channels open and close, leading to irregular heart beat. For a small group of people with heart disease, an irregular heart beat can be dangerous and potentially fatal. Vincenzo Macri is working to determine how the function of pacemaker channels are affected by the flow of sodium and potassium ions. He is using several molecular and cellular experimental approaches, such as patch clamp electrophysiology, DNA mutagenesis, cell culture and cellular imaging to learn about the structure and function of this important protein. By understanding how this process works, he hopes his research may lead to therapies that target these channels to control the onset of irregular heart beats.