Counting Ion and Water Molecules in A Streaming File through the Open-Filter Structure of A K Channel

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Mechanisms underlying selective permeation of ions through channel molecules are a fundamental issue to understand how neurons operate their function. The knock-on mechanism, in which multiple ions in the selectivity filter are hit by an incoming ion, is one of the leading concepts. This mechanism has been supported by crystallographic studies that demonstrated ion distributions in the structure of the KcsA potassium channel. These still pictures under equilibrium conditions, however, may not be a snapshot of on-going permeation processes. To understand dynamics of permeation, here we counted the ratios of ion and water flow (the water-ion coupling ratio: CRw-i) through the KcsA channel by measuring the streaming potential (Vstream) electrophysiologically. Water flow driven by the osmotic pressure flushes out ions in the narrow selectivity filter and generates potential differences across the membrane (Vstream). The Vstream value was converted to the CRw-i value, which tells us how individual ion and water molecules are queued in the narrow and short filter during permeation. At high K+ concentrations, the CRw-i value was 1.0, indicating that turnovers between the alternative ion and water arrays in a single-file undergoes. At low K+, the CRw-i value was increased over 2.2, suggesting that the filter contained mostly one ion at a time. These average behaviors of permeation were kinetically analyzed for more detailed permeating processes. Here we envisioned the permeation as queues of ion and water and sequential transitions between different patterns of arrays. At physiological conditions, we predicted that the “knock-on” mechanism may not be predominant.

Counting Ion and Water Molecules in A Streaming File through the Open-Filter Structure of A K Channel

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