Synaptic facilitation and enhanced neuronal excitability in the submucosal plexus during experimental colitis in guinea-pig
Synaptic facilitation and enhanced neuronal excitability in the submucosal plexus during experimental colitis in guinea-pig
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DOI：
10.1113/jphysiol.2005.084285
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发表时间：
2005-05-01
影响因子：
5.5
通讯作者：
Sharkey, KA
中科院分区：
文献类型：
--
作者：
Lomax, AE;Mawe, GM;Sharkey, KA
肠分泌受肠神经系统的粘膜下神经元调节。肠的炎症导致异常的分泌活动;因此，我们假设粘膜下神经元的突触和电行为在结肠炎期间改变。为了验证这一假设，我们使用细胞内微电极记录比较正常和三硝基苯磺酸（TNBS）发炎豚鼠结肠粘膜下神经元的兴奋性和突触特性。炎症差异影响粘膜下神经元的两个功能类的电生理特性。炎症结肠的AH神经元更易兴奋，动作电位持续时间更短，后超极化减少。结肠炎时，S神经元的刺激诱发快、慢兴奋性突触后电位（EPSP）均增大，且自发性快EPSP的发生率增加。在对照制剂中，快EPSP几乎完全阻断烟碱受体拮抗剂六甲双铵，而快速EPSP在发炎的S神经元只有部分抑制六甲双铵。在炎症组织中，S神经元中的快速EPSP组分对阻断P2（X）和5-HT 3受体敏感，而这些拮抗剂在对照制剂中几乎没有作用。控制和发炎的S神经元同样敏感的乙酰胆碱，ATP和5-HT的短暂应用，这表明突触促进是由于突触前机制。粘膜下神经丛中5-HT的免疫反应性未受炎症影响;这表明改变的突触传递不是由于粘膜下神经末梢的解剖学重塑。这是第一次证明炎症期间肠神经系统突触药理学的改变。
Intestinal secretion is regulated by submucosal neurones of the enteric nervous system. inflammation of the intestines leads to aberrant secretory activity; therefore we hypothesized that the synaptic and electrical behaviours of submucosal neurones are altered during colitis. To test this hypothesis, we used intracellular microelectrode recording to compare the excitability and synaptic properties of submucosal neurones from normal and trinitrobenzene sulphonic acid (TNBS)-inflamed guinea-pig colons. Inflammation differentially affected the electrophysiological characteristics of the two functional classes of submucosal neurones. AH neurones from inflamed colons were more excitable, had shorter action potential durations and reduced afterhyperpolarizations. Stimulus-evoked fast and slow excitatory postsynaptic potentials (EPSPs) in S neurones were larger during colitis, and the incidence of spontaneous fast EPSPs was increased. In control preparations, fast EPSPs were almost completely blocked by the nicotinic receptor antagonist hexamethonium, whereas fast EPSPs in inflamed S neurones were only partially inhibited by hexamethonium. In inflamed tissues, components of the fast EPSP in S neurones were sensitive to blockade of P2(X) and 5-HT3 receptors while these antagonists had little effect in control preparations. Control and inflamed S neurones were equally sensitive to brief application of acetylcholine, ATP and 5-HT, suggesting that synaptic facilitation was due to a presynaptic mechanism. Immunoreactivity for 5-HT in the submucosal plexus was unchanged by inflammation; this indicates that altered synaptic transmission was not due to anatomical remodelling of submucosal nerve terminals. This is the first demonstration of alterations in synaptic pharmacology in the enteric nervous system during inflammation.