Kehl S J, McLennan H, Collingridge G L
Neuroscience. 1984 Jan;11(1):111-24. doi: 10.1016/0306-4522(84)90217-3.
The actions of the neurotoxic amino acids folate and kainate have been compared on ortho-and antidromic responses evoked in CA1, CA3 and the dentate gyrus of slices of rat hippocampus maintained in vitro. Both in CA1 and the dentate gyrus superfusion of these acids caused an increase in amplitude of the population spike discharging from an excitatory postsynaptic potential which either remained unaffected or was reduced. In the CA3 region kainate and folate had broadly similar actions to enhance the probability of cell firing to synaptic excitation, and also caused epileptiform discharges to occur spontaneously or in response to electrical stimulation. Spontaneous and evoked population bursts in CA3 did not persist in low calcium/high magnesium medium indicating their dependence on intact synaptic transmission; spontaneously occurring bursts in CA1 were eliminated with the latter treatment or when the axonal connections between it and CA3 were cut. Following folate superfusion the commissural-evoked response in CA3 showed large and variable shifts of the latency which were dependent on the stimulus intensity and its timing after a spontaneous population discharge. Although all of the effects of folate were reproduced by bicuculline, no evidence for a decreased recurrent inhibition in CA1 was obtained although this was observed with kainate. The finding that folate and kainate produced their effects in the absence of a detectable effect on the antidromic population spike suggests a mechanism of action other than neuronal depolarization. The implications of these data for the neurotoxic mechanism(s) and the receptor homologies of folate and kainate are discussed.
已对神经毒性氨基酸叶酸盐和红藻氨酸在体外培养的大鼠海马切片的CA1、CA3和齿状回中诱发的正向和逆向反应的作用进行了比较。在CA1和齿状回中，这些酸的灌流均导致从兴奋性突触后电位发放的群体峰电位幅度增加，而该电位要么未受影响，要么降低。在CA3区，红藻氨酸和叶酸盐具有大致相似的作用，可增强细胞对突触兴奋的放电概率，还可导致癫痫样放电自发出现或对电刺激产生反应。CA3区的自发和诱发群体爆发在低钙/高镁培养基中不会持续，这表明它们依赖于完整的突触传递；CA1区自发出现的爆发在用后一种处理或切断其与CA3之间的轴突连接时被消除。在灌流叶酸盐后，CA3区联合诱发反应的潜伏期出现大的且可变的变化，这取决于刺激强度及其在自发群体放电后的时间。尽管荷包牡丹碱可重现叶酸盐的所有作用，但未获得CA1区回返抑制减弱的证据，尽管用红藻氨酸时观察到了这种情况。叶酸盐和红藻氨酸在对逆向群体峰电位无明显可检测作用的情况下产生其效应，这一发现提示了一种不同于神经元去极化的作用机制。讨论了这些数据对叶酸盐和红藻氨酸的神经毒性机制及受体同源性的意义。
