The Ahern laboratory is interested in voltage-gated sodium channels as regulators of excitability in nervous and muscle tissue. Our efforts are currently focused on two general topics. First, sodium channels control the upstroke of the action potential in excitable cells making them valuable therapeutic targets in the management of cardiac arrhythmias, epilepsy and pain. We are therefore interested in how sodium-channel inhibitors known as local anesthetics, anti-arrhythmics, and anti-convulsants interact with amino acid side-chains in the channels drug receptor. Our current studies use a combination of site-directed unnatural amino acid mutagenesis and ab initio quantum mechanical calculations to better understand the electrostatic relationships between these cationic drugs and conserved aromatic residues in the channel’s inner vestibule. We also aim to better understand how sodium channels ‘gate’, that is, open, close and inactivate in response to changes in trans-membrane potential. We will enlist a variety of traditional and cutting-edge molecular biological tools for this purpose.
