Ion permeation in K ⁺ channels occurs by direct Coulomb knock-on

Abstract

Potassium channels selectively conduct K + ions across cellular membranes with extraordinary efficiency. Their selectivity filter exhibits four binding sites with approximately equal electron density in crystal structures with high K + concentrations, previously thought to reflect a superposition of alternating ion- and water-occupied states. Consequently, cotranslocation of ions with water has become a widely accepted ion conduction mechanism for potassium channels. By analyzing more than 1300 permeation events from molecular dynamics simulations at physiological voltages, we observed instead that permeation occurs via ion-ion contacts between neighboring K + ions. Coulomb repulsion between adjacent ions is found to be the key to high-efficiency K + conduction. Crystallographic data are consistent with directly neighboring K + ions in the selectivity filter, and our model offers an intuitive explanation for the high throughput rates of K + channels.

Single-file transport of water through membrane channels

“…62,63 Commonly it is believed that the water molecules act as spacers in order to reduce the electrostatic repulsion between the ions. 64 An alternative model that envisioned a water free selectivity lter 65 has not been conrmed experimentally.…”

Multiensemble Markov models of molecular thermodynamics and kinetics

“…We compare the performance of MBAR and TRAM for REMD simulations of solvated alanine dipeptide using 33 exponentially spaced temperatures in the range of 300-600 K (Fig. 3A) 4). To analyze such data with histogram-based methods, one would have to bin the potential energy axis in addition to the coordinate(s) of interest (69).…”

Membrane Transport

“…Recently it has been suggested that potassium ions move sequentially from one site to the next as they march across the membrane, without intervening water molecules. 30,31 However in each case, the selectivity filter determines a high preference for potassium and the channel structure provides a mechanism for potassium ion to move through the channel and across the membrane. …”