RESPONSES TO 5-HT IN MORPHOLOGICALLY IDENTIFIED NEURONS IN THE RAT SUBSTANTIA GELATINOSA IN VITRO

RESPONSES TO 5-HT IN MORPHOLOGICALLY IDENTIFIED NEURONS IN THE RAT SUBSTANTIA GELATINOSA IN VITRO
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DOI:
10.1016/j.neuroscience.2008.12.021
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发表时间:
2009-03-03
期刊:
影响因子:
3.3
通讯作者:
Yoshimura, M.
Yoshimura, M.
中科院分区:
医学3区
文献类型:
--
作者:
Abe, K.;Kato, G.;Yoshimura, M.

文献摘要

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在离体大鼠脊髓胶状质(SG)神经元上,浴用5-HT(1-1000 μ M),在-50 mV的保持膜电位(V-H)下,诱发104/162(64.2%)个抗河豚毒素(TTX)的外向电流。5-HT诱导的外向电流被抑制的外部溶液中含有Ba 2+,或含有Cs2 SO 4和四乙基铵的移液管溶液。在K+通道的平衡电位附近,它被逆转。用含有鸟苷-5-O-(2-硫代二磷酸)-S的移液器溶液形成贴片后30分钟,对5-HT的反应被消除。5-HT诱导的外向电流可被5-HT 1A激动剂(+/-)-8-羟基-2-(二正丙基氨基)四氢萘氢溴酸盐模拟,并被5-HT 1A拮抗剂WAY 100635抑制,提示外向电流中5-HT 1A受体介导的K+通道激活。在11/162(6.8%)的SG神经元中,5-HT产生内向电流,该电流可被5-HT 3激动剂1-(m-chlorophenyl)-biguanide(mCPBG)所模拟。5-HT在垂直细胞(21/34)和小胰岛细胞(11/34)中可诱导外向电流,在胰岛细胞(1/5)和小胰岛细胞(4/5)中可诱导内向电流,而在垂直细胞中不诱导内向电流。已知SG中的大多数垂直细胞和胰岛细胞分别是兴奋性(交感神经能)和抑制性中间神经元,而小胰岛细胞由兴奋性和抑制性神经元组成。应用5-HT或mCPBG可增加自发抑制性突触后电流(sIPSC)的幅度和频率,但无神经元的sIPSC降低。此外,在TTX存在下,5-HT灌注增加了微型IPSC的频率,但幅度没有增加。这些发现,综合起来,表明5-HT诱导外向电流通过5-HT 1A受体兴奋性SG神经元。这些发现还表明,内向电流是突触后和突触前通过5-HT 3受体诱发的,可能在抑制性神经元中。(C)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Bath application of 5-HT (1-1000 mu M) induced a tetrodotoxin (TTX)-resistant outward current at the holding membrane potential (V-H) of -50 mV in 104/162 (64.2%) of substantia gelatinosa (SG) neurons from the rat spinal cord in vitro. The 5-HT-induced outward current was suppressed by an external solution containing Ba2+, or a pipette solution containing Cs2SO4 and tetraethylammonium. It was reversed near the equilibrium potential of the K+ channel. The response to 5-HT was abolished 30 min after patch formation with a pipette solution containing guanosine-5-O-(2-thiodiphosphate)-S. The 5-HT-induced outward current was mimicked by a 5-HT1A agonist, (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide, and suppressed by a 5-HT1A antagonist, WAY100635, suggesting the 5-HT1A receptor-mediated activation of K+ channels in the outward current. In 11/162 (6.8%) SG neurons, 5-HT produced an inward current, which was mimicked by a 5-HT3 agonist, 1-(m-chlorophenyl)-biguanide (mCPBG). The 5-HT-induced outward currents were observed in vertical cells (21/34) and small islet cells (11/34), while inward currents were induced in islet cells (1/5) and small islet (4/5) cells, but not in vertical cells. It is known that most vertical cells and islet cells in the SG are excitatory (glutamatergic) and inhibitory interneurons, respectively, while small islet cells consist of both excitatory and inhibitory neurons. Bath application of 5-HT or mCPBG increased the amplitude and the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), but no neurons showed a decrease in sIPSC. Furthermore, frequency, but not amplitude, of miniature IPSCs increased with perfusion with 5-HT in the presence of TTX. These findings, taken together, suggest that 5-HT induces outward currents through 5-HT1A receptors in excitatory SG neurons. These findings also suggest that the inward currents are post- and presynaptically evoked through 5-HT3 receptors, probably in inhibitory neurons. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.