Department of Anesthesiology, Weill Cornell Medical College, New York, United States; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, United States
Wojciech Wojtas-Niziurski
SIB Swiss Institute of Bioinformatics, University of Basel, Basel, Switzerland; Biozentrum, University of Basel, Basel, Switzerland
Department of Anesthesiology, Weill Cornell Medical College, New York, United States; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, United States; Department of Biochemistry, Weill Cornell Medical College, New York, United States
Potassium channels are opened by ligands and/or membrane potential. In voltage-gated K+ channels and the prokaryotic KcsA channel, conduction is believed to result from opening of an intracellular constriction that prevents ion entry into the pore. On the other hand, numerous ligand-gated K+ channels lack such gate, suggesting that they may be activated by a change within the selectivity filter, a narrow region at the extracellular side of the pore. Using molecular dynamics simulations and electrophysiology measurements, we show that ligand-induced conformational changes in the KcsA channel removes steric restraints at the selectivity filter, thus resulting in structural fluctuations, reduced K+ affinity, and increased ion permeation. Such activation of the selectivity filter may be a universal gating mechanism within K+ channels. The occlusion of the pore at the level of the intracellular gate appears to be secondary.
