Elevated [Cl-]i, and [Na+]i inhibit Na+, K+, Cl- cotransport by different mechanisms in squid giant axons.
Elevated [Cl-]i, and [Na+]i inhibit Na+, K+, Cl- cotransport by different mechanisms in squid giant axons.
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DOI：
10.1085/jgp.107.2.261
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发表时间：
1996-02
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影响因子：
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通讯作者：
Russell JM
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文献类型：
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作者：
Breitwieser GE;Altamirano AA;Russell JM
布美他尼敏感（BS）的单向流量（36）Cl-或（22）Na+测定在内部透析鱿鱼巨轴突，而不同的内部或细胞外浓度的Na+和/或Cl-。提高[Cl-]i或[Na+]i均导致（36）Cl-和（22）Na+的BS内流浓度依赖性减少。提高[Cl-]i高于200 mM完全阻断BS流入。然而，提高[Na+]i至290 mM导致BS Na+流入和BS Cl-流入的饱和但不完全的抑制。不同的细胞内Cl-对协同转运蛋白流出的后果是复杂的。在较低的[Cl-]i值（低于100 mM），细胞内Cl-激活的协同转运蛋白流出。然而，令人惊讶的是，提高[Cl-]i水平> 125 mM导致Na+和Cl-的BS流出的[Cl-] i依赖性抑制。另一方面，提高[Na+]i只导致BS Na+外排的激活;细胞内Na+即使在290 mM也不抑制BS外排。细胞内Na+对协同转运蛋白介导的内流的抑制作用，以及缺乏对BS外排的抑制作用，与预期的有序结合/释放协同转运蛋白操作模型的反式侧抑制一致。然而，细胞内Cl-对流入和流出的抑制作用不能用这样的模型来解释。这些数据表明，Cl可能与细胞内位点（或多个位点）相互作用，其不介导Cl转运，但确实调节Na+、K+、Cl-协同转运蛋白的转运活性。
Bumetanide-sensitive (BS) unidirectional fluxes of (36)Cl- or (22)Na+ were measured in internally dialyzed squid giant axons while varying the intra- or extracellular concentrations of Na+ and/or Cl-. Raising either [Cl-]i or [Na+]i resulted in a concentration-dependent reduction of the BS influx of both (36)Cl- and (22)Na+. Raising [Cl-]i above 200 mM completely blocked BS influxes. However, raising [Na+]i to 290 mM resulted in saturable but incomplete inhibition of both BS Na+ influx and BS Cl- influx. The consequences of varying intracellular Cl- on cotransporter effluxes were complex. At lower [Cl-]i values (below 100 mM) intracellular Cl- activated cotransporter effluxes. Surprisingly, however, raising [Cl-]i levels > 125 mM resulted in a [Cl-]i-dependent inhibition of BS effluxes of both Na+ and Cl-. On the other hand, raising [Na+]i resulted only in the activation of the BS Na+ efflux; intracellular Na+ did not inhibit BS efflux even at 290 mM. The inhibitory effects of intracellular Na+ on cotransporter-mediated influxes, and lack of inhibitory effects on BS effluxes, are consistent with the trans-side inhibition expected for an ordered binding/release model of cotransporter operation. However, the inhibitory effects of intracellular Cl- on both influxes and effluxes are not explained by such a model. These data suggest that Cl may interact with an intracellular site (or sites), which does not mediate Cl transport, but does modulate the transport activity of the Na+, K+, Cl- cotransporter.