EXTRACELLULAR K+ SPECIFICALLY MODULATES A RAT-BRAIN K+ CHANNEL
EXTRACELLULAR K+ SPECIFICALLY MODULATES A RAT-BRAIN K+ CHANNEL
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DOI：
10.1073/pnas.89.6.2466
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发表时间：
1992-03-15
影响因子：
11.1
通讯作者：
STUHMER, W
中科院分区：
文献类型：
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作者：
PARDO, LA;HEINEMANN, SH;STUHMER, W
在所有高等生物中，细胞外钾浓度都被积极地维持在狭窄的范围内。细胞外钾水平的轻微变化可以诱导可兴奋组织的基本生理功能的重大改变。在这里，我们描述了用无钾培养基灌注培养的大鼠海马神经元导致特异性外向钾电流的减少，该电流可能由RCK 4型通道（RCK 4是在大鼠脑中发现的钾通道）携带。这些通道在非洲爪蟾卵母细胞中的异源表达证实了这一点。在该系统中，细胞外钾在生理浓度范围内的变化引起电流幅度的显着差异。此外，在没有细胞外钾的情况下，电流被完全抑制。RCK4通道中宏观电导的钾依赖性通过定点诱变与RCK4蛋白的跨膜区段S5和S6之间的细胞外环中的赖氨酸残基相关，所述赖氨酸残基赋予对四乙基铵的细胞外阻断的抗性。结果表明，细胞外钾影响可用的RCK 4通道的数量，但不影响单通道电导，平均开放时间，或门控电荷位移后去极化。
Extracellular potassium concentration is actively maintained within narrow limits in all higher organisms. Slight variations in extracellular potassium levels can induce major alterations of essential physiological functions in excitable tissues. Here we describe that superfusion of cultured rat hippocampal neurones with potassium-free medium leads to a decrease of a specific outward potassium current, probably carried by RCK4-type channels (RCK4 are potassium channels found in rat brain). This is confirmed by heterologous expression of these channels in Xenopus oocytes. In this system, variations of extracellular potassium in the physiological concentration range induce significant differences in current amplitude. Moreover, the current is completely suppressed in the absence of extracellular potassium. The potassium dependence of macroscopic conductance in RCK4 channels was related by site-directed mutagenesis to that lysine residue in the extracellular loop between the transmembrane segments S5 and S6 of RCK4 protein that confers resistance to extracellular blockage by tetraethylammonium. It is shown that extracellular potassium affects the number of available RCK4 channels, but not the single-channel conductance, the mean open time, or the gating charge displacement upon depolarization.