Billups B, Rossi D, Attwell D
Department of Physiology, University College London, London WC1E 6BT, United Kingdom.
J Neurosci. 1996 Nov 1;16(21):6722-31. doi: 10.1523/JNEUROSCI.16-21-06722.1996.
Glutamate uptake is driven by the cotransport of Na+ ions, the countertransport of K+ ions, and either the countertransport of OH- or the cotransport of H+ ions. In addition, activating glutamate uptake carriers has been shown to lead to activation of an anion conductance present in the carrier structure. Here we characterize the ion selectivity and gating of this anion conductance. The conductance is small with Cl- as the permeant anion, but it is large with NO3- or ClO4- present, undermining the earlier use of NO3- and ClO4- to suggest that OH- countertransport rather than H+ cotransport helps drive uptake. Activation of the anion conductance can be evoked by extra- or intracellular glutamate and can occur even when glutamate transport is inhibited. By running the carrier backward and detecting glutamate release with AMPA receptors in neurons placed near the glial cells, we show that anion flux is not coupled thermodynamically to glutamate movement, but OH-/H+ transport is. The possibility that cell excitability is modulated by the anion conductance associated with glutamate uptake suggests a target for therapeutic drugs to reduce glutamate release in conditions like epilepsy.
谷氨酸摄取由Na⁺离子的协同转运、K⁺离子的反向转运以及OH⁻的反向转运或H⁺离子的协同转运驱动。此外，已表明激活谷氨酸摄取载体可导致载体结构中存在的阴离子电导激活。在此，我们表征了这种阴离子电导的离子选择性和门控特性。当Cl⁻作为通透阴离子时，电导较小，但存在NO₃⁻或ClO₄⁻时电导较大，这削弱了早期使用NO₃⁻和ClO₄⁻来表明OH⁻反向转运而非H⁺协同转运有助于驱动摄取的观点。阴离子电导的激活可由细胞外或细胞内谷氨酸诱发，甚至在谷氨酸转运受到抑制时也可发生。通过使载体反向运行并利用位于神经胶质细胞附近的神经元中的AMPA受体检测谷氨酸释放，我们表明阴离子通量在热力学上与谷氨酸运动不偶联，但OH⁻/H⁺转运是偶联的。与谷氨酸摄取相关的阴离子电导调节细胞兴奋性的可能性提示了治疗药物在癫痫等病症中减少谷氨酸释放的靶点。
