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首页> 外文期刊>The European Journal of Neuroscience >Intracellular acidification in neurons induced by ammonium depends on KCC2 function.
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Intracellular acidification in neurons induced by ammonium depends on KCC2 function.

机译：铵诱导的神经元细胞内酸化取决于KCC2功能。

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摘要

The Cl(-)-extruding neuron-specific K(+)-Cl(-) cotransporter KCC2, which establishes hyperpolarizing inhibition, can transport NH(4) (+) instead of K(+). It is, however, not clear whether KCC2 provides the only pathway for neuronal NH(4) (+) uptake. We therefore investigated NH(4) (+) uptake in cultured rat brain neurons. In neurons cultured for > 4 weeks, the response to NH(4)Cl applications (5 mM) consisted of an alkaline shift which reversed to an acid shift within seconds. Rebound acid shifts which followed brief applications of NH(4)Cl were blocked by furosemide (100 microM). They were rather insensitive to bumetanide (1 and 100 microM), in contrast to those induced in cultured glial cells. Rebound acid shifts persisted in the presence of 1 mM Ba(2+) and in Na(+)-free solution but were inhibited by extracellular K(+). In neurons with depolarizing GABA responses, indicating the absence of functional KCC2, applications of NH(4)Cl barely induced an acidosis. However, large rebound acid shifts occurred in neurons that had changed their GABA response from Ca(2+) increases to Ca(2+) decreases. Rebound acid shifts continued to increase even after the change in the GABA response had occurred and could be induced earlier in neurons transfected with KCC2 cDNA. We conclude that KCC2 provides the main pathway for fast neuronal NH(4) (+) uptake. Therefore, NH(4)Cl-induced rebound acid shifts can be used to indicate the development of KCC2 function. Further, the well known up-regulation of KCC2 function during development has the inevitable consequence of opening a major pathway for NH(4) (+) influx, which can be relevant under pathophysiological conditions.
机译：Cl（-）挤压神经元特定的K（+）-Cl（-）共转运蛋白KCC2，建立超极化抑制，可以转运NH（4）（+）而不是K（+）。然而，尚不清楚是否KCC2提供神经元NH（4）（+）摄取的唯一途径。因此，我们调查了培养的大鼠脑神经元中的NH（4）（+）摄取。在培养> 4周的神经元中，对NH（4）Cl应用程序（5 mM）的响应包括碱转变，其在数秒内反转为酸转变。快速应用NH（4）Cl之后的反弹酸转移被呋塞米（100 microM）阻止。与在培养的神经胶质细胞中诱导的那些相反，它们对布美他尼（1和100 microM）不敏感。反弹的酸移在1 mM Ba（2+）和无Na（+）的溶液中持续存在，但被细胞外K（+）抑制。在具有去极化GABA反应的神经元中，表明没有功能性KCC2，NH（4）Cl的应用几乎不会引起酸中毒。但是，大的反弹酸移位发生在神经元，已经改变了他们的GABA反应从Ca（2+）增加到Ca（2+）减少。即使发生了GABA反应，回弹酸移仍继续增加，并且可以在转染KCC2 cDNA的神经元中更早地诱导回弹酸移。我们得出结论，KCC2提供了快速神经元NH（4）（+）摄取的主要途径。因此，NH（4）Cl诱导的反弹酸移位可用于指示KCC2功能的发展。此外，在开发过程中众所周知的KCC2功能的上调具有不可避免的结果，即为NH（4）（+）流入打开了一条主要途径，这在病理生理条件下可能是相关的。

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