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. T he model is closely based on the gating current studies of the preceding pa per and has been extended to account for ionic current data in the literatu re. We propose that 4AP, like tetraethylammonium ion and other quaternary a mmonium ions, enters and leaves the channel only when the activation gate i s open, a proposal that is strongly supported by the literature. Once in th e open channel, 4AP's major action is to bias the activation gate toward th e closed conformation by approximately the energy of a hydrogen bond. S4 se gment 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 ac tion of quaternary ammonium ions.