Journal of the American Chemical Society, Vol.138, No.32, 10284-10292, 2016
Digitalized K+ Occupancy in the Nanocavity Holds and Releases Queues of K+ in a Channel
The mechanisms of ion permeation through potassium channels have been extensively examined. Molecular 'dynamics (MD) simulations have demonstrated that rapidly permeating ions collide near the selectivity filter (SF) ("knock On" mechanism), but this oversimplified mechanism is insufficient to account for the, experimentally Observed single-channel current amplitudes. Here, we analyzed the MD-simulated ion trajectories through a Kv1.2 potassium channel using an event-oriented analysis method, and surprisingly, we found that the nanocavity (NC) governs ion permeation in a digital fashion. The NC has a maximal diameter of 10 angstrom and stands between the intracellular bulk solution and the SF, which holds only Up to one K+ during permeation. Accordingly, the K+ concentration in the intracellular solution is translated as a digitalized, zero, or one K+ in the NC. When the ion number in the NC is zero, the multiple ions in the SF are mostly immobilized. By contrast, when the number of ions in the NC is one, the structured water in the NC mediates the ion-occupied Status to the queueing ions in the SF, and the ions then initiate a collective outward motion. Accordingly, the one ion in the NC serves as a catalytic intermediate for permeation, which quantitatively accounts for the experimentally obtained conductance-concentration relationships. We conclude that the ion movements are coherent across the entire pore.