The relationship between inflammation-induced neuronal excitability and disrupted motor activity in the guinea pig distal colon
The relationship between inflammation-induced neuronal excitability and disrupted motor activity in the guinea pig distal colon
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DOI：
10.1111/j.1365-2982.2011.01702.x
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发表时间：
2011-07-01
影响因子：
3.5
通讯作者：
Mawe, G. M.
中科院分区：
文献类型：
--
作者：
Hoffman, J. M.;Mcknight, N. D.;Mawe, G. M.
背景结肠炎与后超极化神经元（AH神经元）兴奋性增加和肌间神经丛突触传递易化有关。这些变化伴随着中断推进运动，特别是在溃疡区域。本研究探讨肌间AH神经元过度兴奋和中断推进运动之间的关系。方法应用电压激活Na+通道开放剂藜芦定、中电导钙激活K+通道抑制剂TRAM-34和5-HT 4受体激动剂替加色罗，观察神经元过度兴奋和突触易化对正常豚鼠远端结肠推进运动的影响。由于三硝基苯磺酸（TNBS）结肠炎诱导的肌间传入神经元的过度兴奋性涉及超极化激活的环核苷酸门控（HCN）通道活性的增加，因此使用HCN通道抑制剂Cs+和ZD 7288抑制TNBS结肠炎中的AH神经元活性。关键结果在非炎症制剂中，藜芦碱停止推进运动（P < 0.001）。添加TRAM-34和替加色罗后，推进运动活动率显著降低（P < 0.001）。在TNBS发炎的制剂中，溃疡部位的运动暂时停止或受阻，Cs+和ZD 7288使发炎区域的运动正常化。免疫组织化学研究表明，AH神经元的比例在肌间神经丛溃疡的地区是不变的，但有一个10%的神经元总数减少每个神经节。结论和推论这些研究结果支持的概念，炎症诱导的神经可塑性在肌间神经元，涉及离子通道活性的变化，导致增强AH神经元的兴奋性，可以有助于受损的推进结肠运动。
Background Colitis is associated with increased excitability of afterhyperpolarization neurons (AH neurons) and facilitated synaptic transmission in the myenteric plexus. These changes are accompanied by disrupted propulsive motility, particularly in ulcerated regions. This study examined the relationship between myenteric AH neuronal hyperexcitability and disrupted propulsive motility. Methods The voltage-activated Na+ channel opener veratridine, the intermediate conductance Ca2+-activated K+ channel inhibitor TRAM-34 and the 5-HT4 receptor agonist tegaserod were used to evaluate the effects of neuronal hyperexcitability and synaptic facilitation on propulsive motility in normal guinea pig distal colon. Because trinitrobenzene sulfonic acid (TNBS)-colitis-induced hyperexcitability of myenteric afferent neurons involves increases in hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel activity, the HCN channel inhibitors Cs+ and ZD7288 were used to suppress AH neuronal activity in TNBS-colitis. Key Results In non-inflamed preparations, veratridine halted propulsive motility (P < 0.001). The rate of propulsive motor activity was significantly reduced following addition of TRAM-34 and tegaserod (P < 0.001). In TNBS-inflamed preparations, in which motility was temporarily halted or obstructed at sites of ulceration, both Cs+ and ZD7288 normalized motility through the inflamed regions. Immunohisto-chemistry studies demonstrated that the proportion of AH neurons in the myenteric plexus was unchanged in ulcerated regions, but there was a 10% reduction in total number of neurons per ganglion. Conclusions and Inferences These findings support the concept that inflammation-induced neuroplasticity in myenteric neurons, involving changes in ion channel activity that lead to enhanced AH neuronal excitability, can contribute to impaired propulsive colonic motility.