Dependency of Ion Permeation Pattern on K+ Concentration through the Kv1.2 Channel

It is widely known that ions and water molecules alternately permeate (Pattern A) through the selectivity filter of the K+ channels. However, microscopic mechanisms underlying the exclusive use of the Pattern A remain unsolved. Here we performed the molecular dynamics simulation of ion permeation through the Kv1.2 channel at several different K+ concentrations. We found that the main permeation pattern is, as is expected, Pattern A at all concentrations, while the other kinds of pattern also emerge. At low concentrations, Pattern B, where an ion is transported accompanied with two water molecules, is observed. This behavior is consistent with the recent experiment measuring the streaming potential. On the other hand, Pattern C, where ions are transported without intervening water molecules, is also seen at high concentrations. Pattern C has been reported by some theoretical studies. At the physiological concentration, Pattern B and C, as well as Pattern A, are nearly equally used. In order to clarify why Pattern B and C emerge, the positions of the ions in the selectivity filter were analyzed. In the case of Pattern B, when a next incoming ion approaches the channel, ions are located at the downstream of the selectivity filter, thus two water molecules, having been occupied the selectivity filter, are franked by ions. Once an incoming ion enters into the selectivity filter that bears ions at the upper stream, no water molecule is inserted between the ions, and Pattern C emerges. Thus, the macroscopic observation such as the water-ion coupling ratio reflects differences in the microscopic ion distributions in the selectivity filter at the instance of an upcoming ion enters.