A Furosemide-Sensitive K+–Cl−Cotransporter Counteracts Intracellular Cl− Accumulation and Depletion in Cultured Rat Midbrain Neurons
A Furosemide-Sensitive K+–Cl−Cotransporter Counteracts Intracellular Cl− Accumulation and Depletion in Cultured Rat Midbrain Neurons
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呋塞米敏感的 K+–Cl− 协同转运蛋白可抵消培养的大鼠中脑神经元细胞内 Cl− 的积累和消耗
DOI：
10.1523/jneurosci.19-12-04695.1999
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
U. Misgeld
中科院分区：
文献类型：
--
作者：
W. Jarolimek;A. Lewen;U. Misgeld
哺乳动物大脑中通过 GABAA 受体进行突触后抑制的功效取决于超极化 Cl− 电流的 Cl− 梯度的维持。我们利用了复杂性降低的优势，可以在培养的神经元中研究 Cl- 调节，而不是在哺乳动物大脑的其他体外制剂中的神经元中进行研究。自发 GABAA 受体介导的突触后电流的紧密密封全细胞记录表明，如果细胞体通过贴片吸管加载 Cl-，向外的 Cl- 转运会减少树突 [Cl-]i。我们确定了局部应用 GABA 诱导的 Cl− 电流的树突和体细胞反转电位，以计算贴片移液管中 [K+]o 和 [Cl−] 变化期间的 [Cl−]i。 [Cl−]i 和 [K+]o 通过呋塞米敏感的 K+–Cl− 共转运紧密耦合。热力学考虑排除了 Na+–K+–Cl− 协同转运蛋白对 Cl− 净转运的显着贡献。我们的结论是，在正常[K+]o条件下，K+–Cl−协同转运蛋白有助于将[Cl−]i维持在较低水平，而在病理条件下，[K+]o由于神经元过度活跃而保持升高，协同转运蛋白在神经元中积累Cl−，从而进一步增强神经元兴奋性。
Efficacy of postsynaptic inhibition through GABAAreceptors in the mammalian brain depends on the maintenance of a Cl− gradient for hyperpolarizing Cl− currents. We have taken advantage of the reduced complexity under which Cl− regulation can be investigated in cultured neurons as opposed to neurons in otherin vitro preparations of the mammalian brain. Tightseal whole-cell recording of spontaneous GABAAreceptor-mediated postsynaptic currents suggested that an outward Cl− transport reduced dendritic [Cl−]i if the somata of cells were loaded with Cl− via the patch pipette. We determined dendritic and somatic reversal potentials of Cl− currents induced by focally applied GABA to calculate [Cl−]i during variation of [K+]o and [Cl−] in the patch pipette. [Cl−]i and [K+]o were tightly coupled by a furosemide-sensitive K+–Cl−cotransport. Thermodynamic considerations excluded the significant contribution of a Na+–K+–Cl−cotransporter to the net Cl− transport. We conclude that under conditions of normal [K+]othe K+–Cl− cotransporter helps to maintain [Cl−]i at low levels, whereas under pathological conditions, under which [K+]o remains elevated because of neuronal hyperactivity, the cotransporter accumulates Cl− in neurons, thereby further enhancing neuronal excitability.
DOI：
10.1002/(sici)1097-4695(19971120)33:6
发表时间：
1997-11
期刊：
Journal of neurobiology
影响因子：
--
作者：
M. Plotkin;Evan Y. Snyder;Steven C. Hebert;Eric Delpire
通讯作者：
M. Plotkin;Evan Y. Snyder;Steven C. Hebert;Eric Delpire
影响因子：
2.5
作者：
GROVER, LM;LAMBERT, NA;TEYLER, TJ
通讯作者：
TEYLER, TJ
局麻药QX-314对海马锥体神经元膜特性的影响。
DOI：
--
发表时间：
1982
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Connors,BW;Prince,DA
通讯作者：
Prince,DA