Stringer Janet L, Aribi Ahmed M
Department of Pharmacology and Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3498, USA.
Epilepsy Res. 2003 May;54(2-3):163-70. doi: 10.1016/s0920-1211(03)00064-0.
In the pyramidal cell layer of the CA1 region of the hippocampus in the urethane-anesthetized adult rat, there is an initial alkalinization followed by an acidification in response to synchronized seizure activity induced by stimulus trains. In this study, the role of astrocytes in these extracellular pH changes during neuronal activity was examined using local injection of two relatively selective glial toxins (fluorocitrate (FC) and fluoroacetate (FA)) into the CA1 cell layer. Both glial toxins reduced the peak level of acidification reached after 20 Hz stimulus trains to the contralateral CA3 region, without changing the lengthening of the afterdischarge, when compared to animals that had received a local injection of vehicle. After administration of either glial toxin, the peak level of acidification still correlated with the total discharge duration, but the levels of acidification were consistently lower than in control animals. Administration of either glial toxin had no effect on the peak alkalinization during the stimulus train, or on the rate of recovery from peak level of acidification. Injection of either vehicle, FA, or FC had no effect on the amplitude or frequency of the neuronal discharge during the afterdischarge. The results suggest that, in normal conditions, astrocytes contribute to the acidification of the extracellular space that occurs in response to intense neuronal activity. This acidification may contribute to feedback regulation of neuronal excitability.
在经氨基甲酸乙酯麻醉的成年大鼠海马体CA1区的锥体细胞层中，对由刺激序列诱导的同步癫痫活动会出现初始碱化，随后是酸化。在本研究中，通过向CA1细胞层局部注射两种相对选择性的神经胶质毒素（氟柠檬酸（FC）和氟乙酸（FA）），研究了星形胶质细胞在神经元活动期间这些细胞外pH变化中的作用。与接受局部注射赋形剂的动物相比，两种神经胶质毒素均降低了20 Hz刺激序列后对侧CA3区达到的酸化峰值水平，而不改变后放电的延长时间。给予任何一种神经胶质毒素后，酸化峰值水平仍与总放电持续时间相关，但酸化水平始终低于对照动物。给予任何一种神经胶质毒素对刺激序列期间的峰值碱化或从酸化峰值水平恢复的速率均无影响。注射赋形剂、FA或FC对后放电期间神经元放电的幅度或频率均无影响。结果表明，在正常情况下，星形胶质细胞有助于响应强烈神经元活动而发生的细胞外空间酸化。这种酸化可能有助于神经元兴奋性的反馈调节。
