谷氨酸、海人酸和D-天冬氨酸诱导大鼠海马星形胶质细胞中H⁺和Na⁺变化的机制。
Mechanisms of H+ and Na+ changes induced by glutamate, kainate, and D-aspartate in rat hippocampal astrocytes.
作者信息
Rose C R, Ransom B R
机构信息
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
出版信息
J Neurosci. 1996 Sep 1;16(17):5393-404. doi: 10.1523/JNEUROSCI.16-17-05393.1996.
The excitatory transmitter glutamate (Glu), and its analogs kainate (KA), and D-aspartate (D-Asp) produce significant pH changes in glial cells. Transmitter-induced pH changes in glial cells, generating changes in extracellular pH, may represent a special form of neuronal-glial interaction. We investigated the mechanisms underlying these changes in intracellular H+ concentration ([H+]i) in cultured rat hippocampal astrocytes and studied their correlation with increases in intracellular Na+ concentration ([Na+]i), using fluorescence ratio imaging with 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) or sodium-binding benzofuran isophthalate (SBFI). Glu, KA, or D-Asp evoked increases in [Na+]i; Glu or D-Asp produced parallel acidifications. KA, in contrast, evoked biphasic changes in [H+]i, alkaline followed by acid shifts, which were unaltered after Ca2+ removal and persisted in 0 CI(-)-saline, but were greatly reduced in CO2/HCO3(-)-free or Na(+)-free saline, or during 4,4'-diisothiocyanato-stilbene-2,2'-disulphonic acid (DIDS) application. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked KA-evoked changes in [H+]i and [Na+]i, indicating that they were receptor-ionophore mediated. In contrast, CNQX increased the [H+]i change and decreased the [Na+]i change induced by Glu. D-Asp, which is transported but does not act at Glu receptors, induced [H+]i and [Na+]i changes that were virtually unaltered by CNQX. Our study indicates that [Na+]i increases are not primarily responsible for Glu- or KA-induced acidifications in astrocytes. Instead, intracellular acidifications evoked by Glu or D-Asp are mainly caused by transmembrane movement of acid equivalents associated with Glu/Asp-uptake into astrocytes. KA-evoked biphasic [H+]i changes, in contrast, are probably attributable to transmembrane ion movements mediated by inward, followed by outward, electrogenic Na+/HCO3- cotransport, reflecting KA-induced biphasic membrane potential changes.
兴奋性递质谷氨酸（Glu）及其类似物 kainate（KA）和 D-天冬氨酸（D-Asp）可使神经胶质细胞内的 pH 发生显著变化。递质诱导的神经胶质细胞内 pH 变化进而引起细胞外 pH 改变，这可能代表了一种特殊形式的神经元-神经胶质细胞相互作用。我们利用 2',7'-双（羧乙基）-5,6-羧基荧光素（BCECF）或钠结合苯并呋喃异酞酸酯（SBFI）进行荧光比率成像，研究了培养的大鼠海马星形胶质细胞内 H⁺浓度（[H⁺]i）变化的机制，并探讨了其与细胞内 Na⁺浓度（[Na⁺]i）升高的相关性。Glu、KA 或 D-Asp 均可引起[Na⁺]i 升高；Glu 或 D-Asp 可导致细胞内平行酸化。相比之下，KA 引起[H⁺]i 的双相变化，先是碱性转变，随后是酸性转变，去除 Ca²⁺后这种变化未改变，且在 0 Cl⁻-盐溶液中持续存在，但在无 CO₂/HCO₃⁻或无 Na⁺的盐溶液中，或在应用 4,4'-二异硫氰酸根合芪-2,2'-二磺酸（DIDS）期间，这种变化会大大减少。非 NMDA 受体拮抗剂 6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）可阻断 KA 引起的[H⁺]i 和[Na⁺]i 变化，表明这些变化是由受体-离子通道介导的。相反，CNQX 增加了 Glu 诱导的[H⁺]i 变化，并减少了[Na⁺]i 变化。D-Asp 可被转运但不作用于 Glu 受体，其诱导的[H⁺]i 和[Na⁺]i 变化几乎不受 CNQX 影响。我们的研究表明，[Na⁺]i 升高并非星形胶质细胞中 Glu 或 KA 诱导酸化的主要原因。相反，Glu 或 D-Asp 引起的细胞内酸化主要是由于与 Glu/Asp 摄取到星形胶质细胞相关的酸当量的跨膜移动。相比之下，KA 引起的双相[H⁺]i 变化可能归因于由内向继而外向的电生性 Na⁺/HCO₃⁻共转运介导的跨膜离子移动，这反映了 KA 诱导的双相膜电位变化。
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