Role of Central Cavity in Ion Permeation through the Kv1.2 Channel

Abstract

In the ion permeation pathway of the K+ channel, the narrow selectivity filter is a critical region where ions and water molecules permeate with a single-file fashion. Theoretical studies have been concentrated on the permeation process in the selectivity filter, whereas the role of the central cavity, a common architecture that all the known K+ channels have, is not systematically examined yet. Here we investigated ion permeation through the Kv1.2 channel by the molecular dynamics simulation and analyzed the role of the central cavity. It is found that the central cavity attracts the K+ ions when the ion concentration in the bulk is below the physiological range. Accordingly, the concentration in the central cavity is higher than that in the bulk, increasing the entry chance of ions into the selectivity filter. Thus, the central cavity plays a role to make ion permeation rapid. On the other hand, the ion concentration in the central cavity is found to be saturated at high concentration in the bulk, and the conductance is saturated. These results indicate that the concentration of ions in the central cavity generates the Michaelis-Menten-type behavior of the conductance-concentration curve in the Kv1.2 channel. In contrast, it is known that the saturation of the conductance is not observed in the KcsA channel. We found that the ion concentration in the central cavity increases progressively as the bulk concentration increased up to 2 M, which is in agreement with the apparent non-saturating concentration-conductance curve in the previous studies.