Voltage-gated sodium channels as modulators of electrical excitability in the heart and therapeutic targets in the management of atrial arrhythmias

Electrical disturbances in the heart are a serious health threat for many people. For example, cardiac atrial arrhythmias (a type of irregular heart beat) affect 4% of people aged 60 and older, and have an associated fivefold increase in stroke. As our population ages, this incidence is expected to increase up to 2.5 times over the next half century. Cardiac membrane proteins called ion channels control the flow of sodium and potassium in and out of heart cells, regulating both the cardiac electrical impulses and the contractions associated with the heart beating. Dr. Christopher Ahern is interested in drugs that interact with the sodium ion channel to correct atrial arrhythmias. Although these drugs are widely prescribed, scientists still don’t fully understand exactly how they work. More critical is that these drugs can become lethally toxic in cases where the arrhythmia co-exists with other common heart problems, such as an enlarged heart. This dangerous shortcoming seriously limits their use for many people who could otherwise benefit from their therapeutic effects. There is a need for better anti-arrhythmic therapies – ideally, designer drugs for atrial arrythmias that exploit the positive attributes of current therapies while minimizing their negative side-effects. Dr. Ahern is using new chemical methods that are providing much more detailed information about how these drugs bind to and interact with the sodium channel. Using these new methods in combination with computational approaches that bypass previous limitations with the research, his team will take a fresh look at drug binding and ion channel function with the goal of designing safer anti-arrhythmic drugs