Queueing arrival and release mechanism for K+ permeation through a potassium channel

Abstract

The mechanism underlying ion permeation through potassium channels still remains controversial. K + ions permeate across a narrow selectivity filter (SF) in a single file. Conventional scenarios assume that K + ions are tightly bound in the SF, and, thus, they are displaced from their energy well by ion-ion repulsion with an incoming ion. This tight coupling between entering and exiting ions has been called the "knock-on" mechanism. However, this paradigm is contradicted by experimental data measuring the water-ion flux coupling ratio, demonstrating fewer ion occupancies. Here, the results of molecular dynamics simulations of permeation through the KcsA potassium channel revealed an alternative mechanism. In the aligned ions in the SF (an ion queue), the outermost K + was readily and spontaneously released toward the extracellular space, and the affinity of the relevant ion was ~ 50 mM. Based on this low-affinity regime, a simple queueing mechanism described by loose coupling of entering and exiting ions is proposed.

Conductance selectivity of Na + across the K + channel via Na + trapped in a tortuous trajectory

“…At 0.15 M, two Na + often occupied S3.5 and S1.5 sites, and one ion was sometimes located at S1.5. The same was observed for the K + conduction (31).…”

“…MD Simulation of Na + Permeation through the KcsA Channel. MD simulation allows understanding of the Na + conduction process through the KcsA channel at an atomic scale (31,47). The WT KcsA channel without the cytoplasmic domain was embedded in a lipid bilayer phosphatidylcholine (PC) membrane (Fig.…”

“…4C) do not yield net conduction. Here, we introduce a previously developed mesoscopic model (31) for characterizing the conduction of Na + ensembles. Various configurations of ions in the filter are categorized into a few states by the number of occupied ions in the filter (discrete random variables, see SI Appendix, Fig.…”

“…For example, ion configurations in the plane and cage sites, such as S4-S2.5-S1 and S3.5-S2-S0.5, with three ions in the filter are consolidated into the three-ion-occupied state (State 3; Fig. 5C) (22,31). For the transition from the two-ion-occupied state (State 2) to the three-ion-occupied state (State 3), an ion is supplied from the cavity side.…”

“…filter have been accumulated (30)(31)(32), and a dynamic principle has been proposed as an alternative mechanism for the selectivity (20,33). Simulation studies revealed differential conduction of K + and Na + under different energy profiles, and Burykin et al demonstrated that a different effective charge-charge dielectric for the Na + and K + was a unifying idea of the origin of the selectivity (34)(35)(36).…”