Aribi Ahmed M, Stringer Janet L
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3498, USA.
Epilepsy Res. 2002 Apr;49(2):143-51. doi: 10.1016/s0920-1211(02)00019-0.
Intracellular and extracellular pH are known to influence neuronal activity and may play a role in seizure termination. In the pyramidal cell layer of the CA1 region of the hippocampus in the urethane anesthetized adult rat, there is an initial alkalinization in response to stimulus trains administered to the contralateral CA3 region. This is followed by an acidification that peaks after termination of the afterdischarge. Initial experiments demonstrated that the peak level of acidification correlated with the duration of the afterdischarge, but that the peak level of alkalinization did not. The effects of several antiepileptic drugs on the initial alkalinization were determined. Systemic administration of acetazolamide (50 mg/kg, n=4) and topiramate (45 mg/kg, n=7) and local administration of benzolamide (n=3), all of which inhibit carbonic anhydrase, decreased the initial alkalinization that occurs during the stimulus train. Diazepam (3 mg/kg, n=5) and phenobarbital (60 mg/kg, n=6), agonists at the GABA(A) receptor complex, increased the initial alkalinization, while sodium channel blockers phenytoin (80 mg/kg, n=5) and carbamazepine (50 mg/kg, n=5) had no significant effect. The data suggest that the alkalinization in CA1 in vivo is predominantly regulated through activity of the GABA(A) receptor, rather than through activation of glutamatergic receptors. The change in alkalinization does not appear to be related to the mechanism of the antiepileptic effect of the drugs that were tested.
已知细胞内和细胞外的pH值会影响神经元活动，并可能在癫痫发作终止中发挥作用。在成年大鼠氨基甲酸乙酯麻醉状态下，海马体CA1区的锥体细胞层中，对施加于对侧CA3区的刺激序列会有一个初始碱化反应。随后是酸化，在放电后终止时达到峰值。最初的实验表明，酸化的峰值水平与放电后持续时间相关，但碱化的峰值水平则不然。测定了几种抗癫痫药物对初始碱化的影响。全身给予乙酰唑胺（50mg/kg，n = 4）和托吡酯（45mg/kg，n = 7）以及局部给予苯甲酰胺（n = 3），所有这些药物都抑制碳酸酐酶，降低了刺激序列期间发生的初始碱化。地西泮（3mg/kg，n = 5）和苯巴比妥（60mg/kg，n = 6），GABA(A)受体复合物的激动剂，增加了初始碱化，而钠通道阻滞剂苯妥英（80mg/kg，n = 5）和卡马西平（50mg/kg，n = 5）则没有显著影响。数据表明，体内CA1区的碱化主要通过GABA(A)受体的活性调节，而不是通过谷氨酸能受体的激活。碱化的变化似乎与所测试药物的抗癫痫作用机制无关。
