We are interested in figuring out how ion channels work at the molecular level. We have focused primarily on Ca2+-activated K+ channels; Ca2+ ions bind to a regulatory site on these channels; this binding leads to a conformational change in the channel protein that causes the channel to open. Channel opening lets potassium flow out of the cell; this hyperpolarizes the cell membrane and decreases electrical excitability. In neurons, this translates to a decrease in action potential firing; in vascular smooth muscle, this translates to relaxation, so these channels may be therapeutic targets in the control of blood pressure.
Our strategy to study channel structure and function involves a broad range of techniques, including patch-clamp electrophysiology (to measure the current flow through functional channels), site-directed mutagenesis (to alter individual amino acids in the channel protein), fluorescence spectroscopy (to detect changes in protein conformation), and kinetic analysis and mathematical modeling (to develop working hypothesis of the mechanism underlying channel opening). Projects involve expressing mammalian Ca2+-activated K+ channels in cell lines to study its structure and function, as well as expressing a prokaryotic relative of this channel in bacteria, followed by purification of the channel protein and characterization of the channel using a combination of biochemical and biophysical techniques.