Potassium channels conduct K+ ions rapidly with high selectivity, typically to restore the resting potential of a cell after depolarization by an action potential. Channel activation is usually followed by a spontaneous cessation of ion flow in a process called inactivation. Previously, we have investigated KcsA, a prototypical pH-activated bacterial K+ channel and assessed the thermodynamic basis of the allosteric coupling between the K+-coordinating selectivity filter and the pH-sensing activation gate. Currently, we are pursuing questions related to the role of conformational dynamics in tuning the timescale and energetics of inactivation, as well as the influence of lipid environment and small molecule drugs on these phenomena.
