Control of excitatory synaptic transmission by capsaicin is unaltered in TRPV1 vanilloid receptor knockout mice
Control of excitatory synaptic transmission by capsaicin is unaltered in TRPV1 vanilloid receptor knockout mice
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DOI：
10.1016/j.neuint.2007.06.008
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Hajos, Norbert
中科院分区：
文献类型：
--
作者：
Benninger, Felix;Freund, Tamas F.;Hajos, Norbert
一些研究表明，辣椒素可以有效地调节中枢神经系统的兴奋性突触传递，但这种作用是由TRPV 1香草酸受体（TRPV（1）Rs）介导的假设尚未得到直接验证。为了提供直接证据，我们比较了辣椒素对野生型小鼠和TRPV1R敲除小鼠兴奋性突触的影响。采用全细胞膜片钳技术，在大鼠海马齿状回颗粒细胞记录兴奋性突触后电流（EPSCs）。首先，我们研究了辣椒素对局部刺激分子层纤维诱发的EPSC的影响。在野生型和TRPV1 R基因敲除动物中，10 μ M辣椒素的浴用降低了诱发的EPSC的幅度至相似的程度。用TRPV1R拮抗剂辣椒平（10 μ M）单独或与激动剂辣椒素一起处理切片，也导致野生型和TRPV1R敲除动物EPSC振幅降低。这两种药物似乎影响兴奋性突触在突触前部位的功效，因为观察到药物治疗后EPSC振幅的成对脉冲比显著增加。接下来，我们研究了辣椒素对自发发生的EPSC的影响。这种原型香草素配体增加了野生型小鼠中事件的频率，而不改变其幅度。在TRPV 1R基因敲除小鼠中观察到自发性EPSC频率的类似增强，但幅度没有改变。这些数据强烈反对辣椒素通过激活TRPV（1）Rs（至少在海马网络中）来调节兴奋性突触传递的假设。(C)2007爱思唯尔有限公司保留所有权利。
Several studies have shown that capsaicin could effectively regulate excitatory synaptic transmission in the central nervous system, but the assumption that this effect is mediated by TRPV1 vanilloid receptors (TRPV(1)Rs) has not been tested directly. To provide direct evidence, we compared the effect of capsaicin on excitatory synapses in wild type mice and TRPV1R knockouts. Using whole-cell patch-clamp techniques, excitatory postsynaptic currents (EPSCs) were recorded in granule cells of the dentate gyrus. First, we investigated the effect of capsaicin on EPSCs evoked by focal stimulation of fibers in the stratum moleculare. Bath application of 10 mu M capsaicin reduced the amplitude of evoked EPSCs both in wild type and TRPV1 R knockout animals to a similar extent. Treatment of the slices with the TRPV1R antagonist capsazepine (10 mu M) alone, or together with the agonist capsaicin, also caused a decrease in the EPSC amplitude both in wild type and TRPV1R knockout animals. Both drugs appeared to affect the efficacy of excitatory synapses at presynaptic sites, since a significant increase was observed in paired-pulse ratio of EPSC amplitude after drug treatment. Next we examined the effect of capsaicin on spontaneously occurring EPSCs. This prototypic vanilloid ligand increased the frequency of events without changing their amplitude in wild type mice. Similar enhancement in the frequency without altering the amplitude of spontaneous EPSCs was observed in TRPV1R knockout mice.These data strongly argue against the hypothesis that capsaicin modulates excitatory synaptic transmission by activating TRPV(1)Rs, at least in the hippocampal network. (C) 2007 Elsevier Ltd. All rights reserved.