Use-Dependent Blockers and Exit Rate of the Last Ion from the Multi-Ion Pore of a K + Channel

• DOI: 10.1126/science.271.5249.653
• Publication Date: 2006-10-27T18:30:41Z
• Authors: Thomas Baukrowitz; Gary Yellen
• Keywords: Quaternary Ammonium Compounds; 0301 basic medicine; 03 medical and health sciences; Binding Sites; Potassium Channels; Potassium; Potassium Channel Blockers; Shaker Superfamily of Potassium Channels; Humans; Lidocaine; Tetraethylammonium Compounds; Cell Line

Quaternary ammonium blockers inhibit many voltage-activated potassium (K + ) channels from the intracellular side. When applied to Drosophila Shaker potassium channels expressed in mammalian cells, these rapidly reversible blockers produced use-dependent inhibition through an unusual mechanism-they promoted an intrinsic conformational change known as C-type inactivation, from which recovery is slow. The blockers did so by cutting off potassium ion flow to a site in the pore, which then emptied at a rate of 10 5 ions per second. This slow rate probably reflected the departure of the last ion from the multi-ion pore: Permeation of ions (at 10 7 per second) occurs rapidly because of ion-ion repulsion, but the last ion to leave would experience no such repulsion.