Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
Neurogastroenterol Motil. 2012 Jan;24(1):e41-55. doi: 10.1111/j.1365-2982.2011.01806.x. Epub 2011 Nov 10.
Intramuscular interstitial cells of Cajal (ICC-IM) have been shown to participate in nitrergic neuromuscular transmission (NMT) in various regions of the gastrointestinal (GI) tract, but their role in the internal anal sphincter (IAS) is still uncertain. Contractile studies of the IAS in the W/W(v) mouse (a model in which ICC-IM numbers are markedly reduced) have reported that nitrergic NMT persists and that ICC-IM are not required. However, neither the changes in electrical events underlying NMT nor the contributions of other non-nitrergic neural pathways have been examined in this model.
The role of ICC-IM in NMT was examined by recording the contractile and electrical events associated with electrical field stimulation (EFS) of motor neurons in the IAS of wildtype and W/W(v) mice. Nitrergic, purinergic, and cholinergic components were identified using inhibitors of these pathways.
Under NANC conditions, purinergic and nitrergic pathways both contribute to EFS-induced inhibitory junction potentials (IJPs) and relaxation. Purinergic IJPs and relaxation were intact in the W/W(v) mouse IAS, whereas nitrergic IJPs were reduced by 50-60% while relaxation persisted. In the presence of L-NNA (NOS inhibitor) and MRS2500 (P2Y1 receptor antagonist), EFS gave rise to cholinergic depolarization and contractions that were abolished by atropine. Cholinergic depolarization was absent in the W/W(v) mouse IAS while contraction persisted.
CONCLUSIONS & INFERENCES: ICC-IM significantly contributes to the electrical events underlying nitrergic and cholinergic NMT, whereas contractile events persist in the absence of ICC-IM. The purinergic inhibitory neural pathway appears to be independent of ICC-IM.
已经表明，Cajal 间质细胞（ICC-IM）在内脏肌间神经丛中参与了各种胃肠道（GI）区域的氮能神经肌肉传递（NMT），但其在肛门内括约肌（IAS）中的作用仍不确定。在 W/W（v）小鼠（ICC-IM 数量明显减少的模型）的 IAS 收缩研究报告称，氮能 NMT 仍然存在，并且 ICC-IM 不是必需的。然而，在该模型中，尚未检查 NMT 潜在电事件的变化以及其他非氮能神经通路的贡献。
通过记录与电刺激运动神经元相关的电活动和收缩活动，来研究 ICC-IM 在 NMT 中的作用，该电刺激作用于野生型和 W/W（v）小鼠的 IAS。使用这些途径的抑制剂来鉴定氮能、嘌呤能和胆碱能成分。
在 NANC 条件下，嘌呤能和氮能途径都有助于 EFS 诱导的抑制性突触后电位（IJPs）和松弛。W/W（v）小鼠 IAS 中的嘌呤能 IJPs 和松弛保持完整，而氮能 IJPs 减少了 50-60%，而松弛仍然存在。在 L-NNA（NOS 抑制剂）和 MRS2500（P2Y1 受体拮抗剂）存在的情况下，EFS 引起胆碱能去极化和收缩，而去极化被阿托品消除。在 W/W（v）小鼠 IAS 中，胆碱能去极化不存在，而收缩仍然存在。
ICC-IM 显著促进氮能和胆碱能 NMT 的电活动，而 ICC-IM 缺失时收缩仍然存在。嘌呤能抑制性神经通路似乎独立于 ICC-IM。
