Taira T, Smirnov S, Voipio J, Kaila K
Department of Zoology, University of Helsinki, Finland.
Neuroreport. 1993 Jan;4(1):93-6. doi: 10.1097/00001756-199301000-00024.
Recent work suggests that activity-induced alkaline transients within the interstitial space of nervous tissue are largely due to net fluxes of acid-base equivalents across postsynaptic receptor-gated ion channels. In view of the marked pH sensitivity of certain receptor channels, it has been frequently postulated that synaptically-evoked H+ shifts might play a neuromodulatory role. We provide here the first evidence to support the above hypothesis in showing that extracellularly recorded glutamatergic responses in area CA1 of rat hippocampal slices are potentiated upon inhibition of fast extracellular H+ buffering by a poorly-permeant carbonic anhydrase inhibitor, benzolamide (10 microM). Experiments with glutamate receptor antagonists and Mg(2+)-free solutions suggest that the action of benzolamide is mediated by the H+ sensitivity of N-methyl-D-aspartate (NMDA) receptor channels. In further agreement with an intrinsic neuromodulatory role for H+ in excitatory transmission, addition of the H+ buffer HEPES (20 mM) produced a selective attenuation of pharmacologically-isolated NMDA receptor-mediated responses.
最近的研究表明，神经组织间隙内由活动诱导的碱性瞬变主要是由于酸碱当量跨突触后受体门控离子通道的净通量所致。鉴于某些受体通道对pH值具有显著的敏感性，人们经常推测突触诱发的H⁺转移可能发挥神经调节作用。我们在此提供首个证据支持上述假设，即通过一种低渗透性碳酸酐酶抑制剂苯甲酰胺（10微摩尔）抑制细胞外快速H⁺缓冲后，大鼠海马切片CA1区细胞外记录的谷氨酸能反应增强。使用谷氨酸受体拮抗剂和无镁溶液进行的实验表明，苯甲酰胺的作用是由N-甲基-D-天冬氨酸（NMDA）受体通道对H⁺的敏感性介导的。进一步支持H⁺在兴奋性传递中具有内在神经调节作用的是，添加H⁺缓冲剂4-(2-羟乙基)-1-哌嗪乙磺酸（HEPES，20毫摩尔）会使药理学分离的NMDA受体介导的反应选择性减弱。
