A model for 4-aminopyridine action on K channels: similarities to tetraethylammonium ion action

We present a model for the action of 4-aminopyridine (4AP) on K channels. The model is closely based on the gating current studies of the preceding paper and has been extended to account for ionic current data in the literature. We propose that 4AP, like tetraethylammonium ion and other quaternary ammonium ions, enters and leaves the channel only when the activation gate is open, a proposal that is strongly supported by the literature. Once in the open channel, 4AP's major action is to bias the activation gate toward the closed conformation by approximately the energy of a hydrogen bond. S4 segment movement, as reflected in gating currents, is almost normal for a 4AP-occupied channel; only the final opening transition is affected. The model is qualitatively the same as the one used for many years to explain the action of quaternary ammonium ions.