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

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Science  02 Feb 1996:
Vol. 271, Issue 5249, pp. 653-656
DOI: 10.1126/science.271.5249.653


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 105 ions per second. This slow rate probably reflected the departure of the last ion from the multi-ion pore: Permeation of ions (at 107 per second) occurs rapidly because of ion-ion repulsion, but the last ion to leave would experience no such repulsion.