Investigating the biophysics and structural basis for state dependent drug blockade of persistent/late sodium current (INa(P)) in the heart using photoactivatable crosslinking unnatural amino acids.
Electrical activity in the heart is controlled by the concerted activity of many proteins called ion-channels that regulate the transfer of different ions across cell membranes. Recently, researchers in biomedical science have identified that a particular component of sodium carrying ion-channel activity (called the persistent or late sodium current also known as (INa(P)) played a major role in controlling the electrical activity of the heart. More recent research suggests that this late sodium current may be involved in various cardiac diseases. This research project seeks to understand and define the mechanisms by which the late sodium current arises and how drugs block this current. This is of great benefit to Cardiome, our industrial partner, because it will allow them to understand the states through which ion channels must pass to generate their currents, and help guide the application of this science toward the invention and development of novel therapeutics.