SEGMENTAL EXCHANGES DEFINE 4-AMINOPYRIDINE BINDING AND THE INNER MOUTH OF K+ PORES
SEGMENTAL EXCHANGES DEFINE 4-AMINOPYRIDINE BINDING AND THE INNER MOUTH OF K+ PORES
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DOI：
10.1016/0896-6273(93)90154-j
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发表时间：
1993-09-01
期刊：
影响因子：
16.2
通讯作者：
BROWN, AM
中科院分区：
文献类型：
--
作者：
KIRSCH, GE;SHIEH, CC;BROWN, AM
4-氨基吡啶（4AP）阻断电压门控K+通道的细胞内口。我们确定了4AP与嵌合通道结合的关键区域，在嵌合通道中， 低亲和力克隆（Kv2.1，IC 50 = 18 mM）替换为高亲和力克隆（Kv3.1，IC 50 = 0.1 mM）。4AP敏感性不随S5-S6接头（孔或P区）转移。相反，嵌合体的细胞质一半的S6增加块20倍，而不影响门控。S5和S6的胞质一半的双嵌合体完全转移4AP敏感性。由于4AP块抑制tetrapentylammonium，我们得出结论，4AP结合的决定因素在于S6段，形成的孔的细胞质前庭，这个网站可能会重叠季铵网站。
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, IC50 = 18 mM) were replaced with those of a high affinity clone (Kv3.1, IC50 = 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.