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• Articles by J.Z. Yeh
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• Segmental exchanges define 4-aminopyridine binding and the i...

  Segmental exchanges define 4-aminopyridine binding and the inner mouth of K pores Neuron, Volume 11, Issue 3, 1 September 1993, Pages 503-512 G.E. Kirsch, C.-C. Shieh, J.A. Drewe, D.F. Vener and A.M. Brownt Summary 4-Aminopyridine (4AP) blocks the intracellular mouth of voltage-gated K channels. We identified critical regions for 4AP binding with chimeric channels in which segments of a low affinity clone (Kv2.1, IC = 18 mM) were replaced with those of a high affinity clone (Kv3.1, IC = 0.1 mM) 4AP sensitivity was not tranferred with the S5–S6 linker (pore or P region) Instead, a chimera of the cytoplasmic half of S6 increased block 20-fold, without affecting gating.A double chimera of the cytoplasmic halves of S5 and S6 fully transferred 4AP sensitivity. Because 4AP block was inhibited by tetrapentylammonium, we conclude that determinants of 4AP binding lie in the S6 segment that forms the cytoplasmic vestibule of the pore and that this site may overlap a quaternary ammonium site. Summary | PDF (1134 kb)

• Modulation of aminopyridine block of potassium currents in s...

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• Inactivation and Pharmacological Properties of sqKv1A Homote...

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Abstract

The effects of aminopyridines on ionic conductances of the squid giant axon membrane were examined using voltage clamp and internal perfusion techniques. 4-Aminopyridine (4-AP) reduced potassium currents, but had no effect upon transient sodium currents. The block of potassium channels by 4-AP was substantially less with (a) strong depolarization to positive membrane potentials, (b) increasing the duration of a given depolarizing step, and (c) increasing the frequency of step depolarizations. Experiments with high external potassium concentrations revealed that the effect of 4-AP was independent of the direction of potassium ion movement. Both 3- and 2-aminopyridine were indistinguishable from 4-AP except in potency. It is concluded that aminopyrimidines may be used as tools to block the potassium conductance in excitable membranes, but only within certain specific voltage and frequency limits.