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Biophys J. Aug 2001; 81(2): 895–904.
PMCID: PMC1301561

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.

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Selected References

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  • Armstrong CM. Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. J Gen Physiol. 1971 Oct;58(4):413–437. [PMC free article] [PubMed]
  • Bezanilla F, Armstrong CM. Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons. J Gen Physiol. 1972 Nov;60(5):588–608. [PMC free article] [PubMed]
  • Bever CT, Jr, Anderson PA, Leslie J, Panitch HS, Dhib-Jalbut S, Khan OA, Milo R, Hebel JR, Conway KL, Katz E, et al. Treatment with oral 3,4 diaminopyridine improves leg strength in multiple sclerosis patients: results of a randomized, double-blind, placebo-controlled, crossover trial. Neurology. 1996 Dec;47(6):1457–1462. [PubMed]
  • del Camino D, Holmgren M, Liu Y, Yellen G. Blocker protection in the pore of a voltage-gated K+ channel and its structural implications. Nature. 2000 Jan 20;403(6767):321–325. [PubMed]
  • Demo SD, Yellen G. The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker. Neuron. 1991 Nov;7(5):743–753. [PubMed]
  • Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science. 1998 Apr 3;280(5360):69–77. [PubMed]
  • Fujihara K, Miyoshi T. The effects of 4-aminopyridine on motor evoked potentials in multiple sclerosis. J Neurol Sci. 1998 Jul 15;159(1):102–106. [PubMed]
  • Holmgren M, Smith PL, Yellen G. Trapping of organic blockers by closing of voltage-dependent K+ channels: evidence for a trap door mechanism of activation gating. J Gen Physiol. 1997 May;109(5):527–535. [PMC free article] [PubMed]
  • Kirsch GE, Drewe JA. Gating-dependent mechanism of 4-aminopyridine block in two related potassium channels. J Gen Physiol. 1993 Nov;102(5):797–816. [PMC free article] [PubMed]
  • Kirsch GE, Narahashi T. Site of action and active form of aminopyridines in squid axon membranes. J Pharmacol Exp Ther. 1983 Jul;226(1):174–179. [PubMed]
  • Kirsch GE, Shieh CC, Drewe JA, Vener DF, Brown AM. Segmental exchanges define 4-aminopyridine binding and the inner mouth of K+ pores. Neuron. 1993 Sep;11(3):503–512. [PubMed]
  • Kirsch GE, Yeh JZ, Oxford GS. Modulation of aminopyridine block of potassium currents in squid axon. Biophys J. 1986 Oct;50(4):637–644. [PMC free article] [PubMed]
  • Loboda A, Armstrong CM. Resolving the gating charge movement associated with late transitions in K channel activation. Biophys J. 2001 Aug;81(2):905–916. [PMC free article] [PubMed]
  • McCormack K, Joiner WJ, Heinemann SH. A characterization of the activating structural rearrangements in voltage-dependent Shaker K+ channels. Neuron. 1994 Feb;12(2):301–315. [PubMed]
  • Melishchuk A, Armstrong CM. Mechanism underlying slow kinetics of the OFF gating current in Shaker potassium channel. Biophys J. 2001 May;80(5):2167–2175. [PMC free article] [PubMed]
  • Smith KJ, Felts PA, John GR. Effects of 4-aminopyridine on demyelinated axons, synapses and muscle tension. Brain. 2000 Jan;123(Pt 1):171–184. [PubMed]

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