One of the most significant barriers that is currently impeding the development of new anti-arrhythmic drugs is the complexity of the electrical control system that tells the heart when to beat. The reason that this system is so complex is that there are many scales from nanometers to centimeters and from nanoseconds to seconds. This means that a nanoscale change can cause or prevent deadly arrhythmias. Our goal is to create computational models to connect these scales. Our hope is that by mathematically defining these connections, we will be able to discover new therapeutic targets to treat arrhythmia patients.
Watching Ion Channels Move
Voltage-clamp fluorometry is a recent technique in which fluorescence from a specific protein site and ionic current are tracked simultaneously to infer mechanism. We’re the first lab to obtain this type of recording from the cardiac Na+ channel (shown below).
Moving forward, we can introduce:
- pathogenic mutations to see their effect on channel function,
- pharmaceuticals to see how drug block alters voltage sensor movement,
- accessory proteins and subunits to look at channel regulation.