Barbour B, Brew H, Attwell D
Department of Physiology, University College London, UK.
Nature. 1988 Sep 29;335(6189):433-5. doi: 10.1038/335433a0.
Uptake of glutamate into glial cells in the CNS maintains the extracellular glutamate concentration below neurotoxic levels and helps terminate its action as a neurotransmitter. The co-transport of two sodium ions on the glutamate carrier is thought to provide the energy needed to transport glutamate into cells. We have shown recently that glutamate uptake can be detected electrically because the excess of Na+ ions transported with each glutamate anion results in a net current flow into the cell. We took advantage of the control of the environment, both inside and outside the cell, provided by whole-cell patch-clamping and now report that glutamate uptake is activated by intracellular potassium and inhibited by extracellular potassium. Our results indicate that one K+ ion is transported out of the cell each time a glutamate anion and three Na+ ions are transported in. A carrier with this stoichiometry can accumulate glutamate against a much greater concentration gradient than a carrier co-transporting one glutamate anion and two Na+ ions. Pathological rises in extracellular potassium concentration will inhibit glutamate uptake by depolarizing glial cells and by preventing the loss of K+ from the glutamate carrier. This will facilitate a rise in the extracellular glutamate concentration to neurotoxic levels and contribute to the neuronal death occurring in brain anoxia and ischaemia.
中枢神经系统中，胶质细胞摄取谷氨酸可使细胞外谷氨酸浓度维持在神经毒性水平以下，并有助于终止其作为神经递质的作用。谷氨酸载体上两个钠离子的协同转运被认为提供了将谷氨酸转运到细胞内所需的能量。我们最近发现，可以通过电检测谷氨酸摄取，因为每个谷氨酸阴离子转运时伴随的过量钠离子会导致净电流流入细胞。我们利用全细胞膜片钳技术对细胞内外环境的控制，现在报告谷氨酸摄取受细胞内钾离子激活，受细胞外钾离子抑制。我们的结果表明，每次转运一个谷氨酸阴离子和三个钠离子进入细胞时，会有一个钾离子从细胞内转运出去。与协同转运一个谷氨酸阴离子和两个钠离子的载体相比，具有这种化学计量关系的载体能够逆着更大的浓度梯度积累谷氨酸。细胞外钾离子浓度的病理性升高会通过使胶质细胞去极化以及阻止钾离子从谷氨酸载体上流失来抑制谷氨酸摄取。这将促使细胞外谷氨酸浓度升高至神经毒性水平，并导致脑缺氧和缺血时发生的神经元死亡。
