α7 nicotinic acetylcholine receptors and modulation of gabaergic synaptic transmission in the hippocampus
α7 nicotinic acetylcholine receptors and modulation of gabaergic synaptic transmission in the hippocampus
复制标题
DOI：
10.1016/s0014-2999(00)00006-6
复制
发表时间：
2000-03-30
影响因子：
5
通讯作者：
Albuquerque, EX
中科院分区：
文献类型：
--
作者：
Alkondon, M;Braga, MFM;Albuquerque, EX
本文报道了大鼠海马片CA1中间神经元α7烟碱受体活性对γ-氨基丁酸传递的调节作用。记录是从紧密密封的CA1中间神经元细胞贴片中获得的，激动剂通过改进的U管输送到神经元。将α7烟碱受体选择性激动剂胆碱(大于或等于1 mM)的6 S作用于所有被测的CA1区中间神经元，触发动作电位被检测为快电流瞬变。由胆碱触发的活动早在激动剂脉冲结束前就终止了，被α7烟碱受体拮抗剂甲基鸟苷(50 NM)阻断，并具有浓度依赖性；胆碱浓度越高，事件发生的频率越高，第一次事件的检测延迟越短。在40%的被测试神经元中，胆碱触发的动作电位的幅度逐渐降低，直到尽管存在激动剂也无法检测到更多的事件。这一发现主要可以通过与α7烟碱受体激活引起的膜去极化相关的Na+通道失活来解释。在60%的神经元中，胆碱诱导的动作电位的幅度维持在初始水平，但同样地，这种活动没有持续到激动剂脉冲那么长的时间，在这种情况下，显然是由于激动剂诱导的受体脱敏。这些结果表明，与α7烟碱受体相互作用的激动剂，包括天然递质乙酰胆碱及其代谢物胆碱，不仅通过激活这些受体，而且通过控制Na+通道失活和/或通过诱导受体脱敏来影响GABA能传递。(C)2000 Elsevier Science B.V.保留所有权利。
The present report provides new findings regarding modulation of gamma-aminobutyric acid (GABA) transmission by alpha 7 nicotinic receptor activity in CA1 interneurons of rat hippocampal slices. Recordings were obtained from tight-seal cell-attached patches of the CA1 interneurons, and agonists were delivered to the neurons via a modified U-tube. Application for 6 s of the alpha 7 nicotinic receptor-selective agonist choline (greater than or equal to 1 mM) to all CA1 interneurons tested triggered action potentials that were detected as fast current transients. The activity triggered by choline terminated well before the end of the agonist pulse, was blocked by the alpha 7 nicotinic receptor antagonist methyllycaconitine (50 nM) and was concentration dependent; the higher the concentration of choline the higher the frequency of events and the shorter the delay for detection of the first event. In 40% of the neurons tested, choline-triggered action potentials decreased in amplitude progressively until no more events could be detected despite the presence of the agonist. Primarily, this finding could be explained by Na+-channel inactivation associated with membrane depolarization induced by alpha 7 nicotinic receptor activation. In 60% of the neurons, the amplitude of choline-induced action potentials was sustained at the initial level, but again the activity did not last as long as the agonist pulse, in this case apparently because of agonist-induced receptor desensitization. These results altogether demonstrate that agonists interacting with alpha 7 nicotinic receptors, including the natural transmitter acetylcholine and its metabolite choline, influence GABAergic transmission, not only by activating these receptors, but also by controlling the rate of Na+-channel inactivation and/or by inducing receptor desensitization. (C) 2000 Elsevier Science B.V. All rights reserved.