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

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.