Institute of Clinical Chemistry, University Hospital Jena, Friedrich Schiller University Jena, D-07747 Jena, Germany.
J Neurosci. 2011 May 18;31(20):7300-11. doi: 10.1523/JNEUROSCI.0269-11.2011.
On the one hand, neuronal activity can cause changes in pH; on the other hand, changes in pH can modulate neuronal activity. Consequently, the pH of the brain is regulated at various levels. Here we show that steady-state pH and acid extrusion were diminished in cultured hippocampal neurons of mice with a targeted disruption of the Na(+)-driven Cl(-)/HCO(3)(-) exchanger Slc4a8. Because Slc4a8 was found to predominantly localize to presynaptic nerve endings, we hypothesize that Slc4a8 is a key regulator of presynaptic pH. Supporting this hypothesis, spontaneous glutamate release in the CA1 pyramidal layer was reduced but could be rescued by increasing the intracellular pH. The reduced excitability in vitro correlated with an increased seizure threshold in vivo. Together with the altered kinetics of stimulated synaptic vesicle release, these data suggest that Slc4a8 modulates glutamate release in a pH-dependent manner.
一方面，神经元活动会引起 pH 值的变化；另一方面，pH 值的变化可以调节神经元活动。因此，大脑的 pH 值在多个水平上受到调节。在这里，我们展示了在具有靶向破坏 Na(+)-驱动的 Cl(-)/HCO(3)(-)交换体 Slc4a8 的小鼠培养的海马神经元中，稳态 pH 值和酸外排减少。由于 Slc4a8 主要定位于突触前神经末梢，我们假设 Slc4a8 是突触前 pH 值的关键调节剂。支持这一假设，CA1 锥体层中的自发谷氨酸释放减少，但通过增加细胞内 pH 值可以挽救。体外兴奋性降低与体内癫痫发作阈值升高相关。结合刺激的突触小泡释放的动力学改变，这些数据表明 Slc4a8 以 pH 依赖的方式调节谷氨酸释放。
