Debonnel G, Beauchesne L, de Montigny C
Institut Philippe Pinel de Montréal, Québec, Canada.
Can J Physiol Pharmacol. 1989 Jan;67(1):29-33. doi: 10.1139/y89-005.
Domoic acid, an excitatory amino acid structurally related to kainate, was recently identified as being presumably responsible for the recent severe intoxication presented by more than 100 people having eaten mussels grown in Prince Edward Island (Canada). The amino acid kainate has been shown to be highly neurotoxic to the hippocampus, which is the most sensitive structure in the central nervous system. The present in vivo electrophysiological studies were undertaken to determine if domoic acid exerts its neurotoxic effect via kainate receptor activation. Unitary extracellular recordings were obtained from pyramidal neurons of the CA1 and the CA3 regions of the rat dorsal hippocampus. The excitatory effect of domoic acid applied by microiontophoresis was compared with that of agonists of the three subtypes of glutamatergic receptors: kainate, quisqualate, and N-methyl-D-aspartate. In CA1, the activation induced by domoic acid was about threefold greater than that induced by kainate; identical concentrations and similar currents were used. In CA3, domoic acid was also three times more potent than kainate. However, the most striking finding was that domoic acid, similar to kainate, was more than 20-fold more potent in the CA3 than in the CA1 region, whereas no such regional difference could be detected with quisqualate and N-methyl-D-aspartate. As the differential regional response of CA1 and CA3 pyramidal neurons to kainate is attributable to the extremely high density of kainate receptors in the CA3 region, these results provide the first electrophysiological evidence that domoic acid may produce its neurotoxic effects through kainate receptor activation.
软骨藻酸是一种在结构上与海人酸相关的兴奋性氨基酸，最近被确定可能是导致100多名食用了生长于加拿大爱德华王子岛的贻贝的人出现严重中毒事件的原因。海人酸已被证明对海马体具有高度神经毒性，而海马体是中枢神经系统中最敏感的结构。进行目前这项体内电生理研究是为了确定软骨藻酸是否通过激活海人酸受体发挥其神经毒性作用。从大鼠背侧海马体CA1和CA3区的锥体神经元获取单细胞胞外记录。将通过微离子电泳施加的软骨藻酸的兴奋作用与三种谷氨酸能受体亚型（海人酸、quisqualate和N-甲基-D-天冬氨酸）的激动剂的兴奋作用进行比较。在CA1区，软骨藻酸诱导的激活作用比海人酸诱导的激活作用大约大三倍；使用的是相同浓度和相似电流。在CA3区，软骨藻酸的效力也比海人酸高三倍。然而，最显著的发现是，与海人酸类似，软骨藻酸在CA3区的效力比在CA1区高20多倍，而quisqualate和N-甲基-D-天冬氨酸未检测到这种区域差异。由于CA1和CA3锥体神经元对海人酸的区域反应差异归因于CA3区海人酸受体的极高密度，这些结果提供了首个电生理证据，表明软骨藻酸可能通过激活海人酸受体产生其神经毒性作用。
