Interstitial cells of Cajal mediate nitrergic inhibitory neurotransmission in the murine gastrointestinal tract
Interstitial cells of Cajal mediate nitrergic inhibitory neurotransmission in the murine gastrointestinal tract
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DOI：
10.1152/ajpgi.00082.2014
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发表时间：
2014-07-01
影响因子：
4.5
通讯作者：
Friebe, Andreas
中科院分区：
文献类型：
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作者：
Lies, Barbara;Gil, Victor;Friebe, Andreas
一氧化氮 (NO) 是胃肠道 (GI) 中的主要抑制性神经递质。其主要效应物 NO 敏感鸟苷酸环化酶 (NO-GC) 在多种胃肠道细胞类型中表达，包括平滑肌细胞 (SMC)、卡哈尔间质细胞 (ICC) 和成纤维细胞样细胞。迄今为止，神经元和这些细胞之间启动氮能抑制连接电位（IJP）的相互作用尚不清楚。在这里，我们研究了小鼠眼底和结肠中氮能 IJP 的起源。在全面缺乏 NO-GC (GCKO) 的小鼠的眼底和结肠 SMC 中测定了 IJP，特别是在 SMC (SM-GCKO)、ICC (ICC-GCKO) 和 SMC/ICC (SM/ICC-GCKO) 中。 ICC-GCKO 眼底中氮能 IJP 被取消，SM-GCKO 眼底中氮能 IJP 减少。在结肠中，ICC-GCKO 中氮能 IJP 的幅度降低，而 SM-GCKO 中氮能 IJP 的持续时间降低。全球 GCKO 中氮能 IJP 的缺失证实了这些结果。总之，我们的结果证明了 NO-GC 在 ICC 中对于启动 IJP 的必要作用。 SMC 中的 NO-GC 似乎增强了氮能 IJP，分别导致眼底和结肠 SMC 中更强且更长时间的超极化。因此，两种细胞类型中的 NO-GC 对于诱导完全氮能 IJP 是必需的。我们来自结肠的数据清楚地表明，氮能 IJP 是双相的，由 ICC 和 SMC 的单独输入产生。
Nitric oxide (NO) is a major inhibitory neurotransmitter in the gastrointestinal (GI) tract. Its main effector, NO-sensitive guanylyl cyclase (NO-GC), is expressed in several GI cell types, including smooth muscle cells (SMC), interstitial cells of Cajal (ICC), and fibroblast-like cells. Up to date, the interplay between neurons and these cells to initiate a nitrergic inhibitory junction potential (IJP) is unclear. Here, we investigate the origin of the nitrergic IJP in murine fundus and colon. IJPs were determined in fundus and colon SMC of mice lacking NO-GC globally (GCKO) and specifically in SMC (SM-GCKO), ICC (ICC-GCKO), and both SMC/ICC (SM/ICC-GCKO). Nitrergic IJP was abolished in ICC-GCKO fundus and reduced in SM-GCKO fundus. In the colon, the amplitude of nitrergic IJP was reduced in ICC-GCKO, whereas nitrergic IJP in SM-GCKO was reduced in duration. These results were corroborated by loss of the nitrergic IJP in global GCKO. In conclusion, our results prove the obligatory role of NO-GC in ICC for the initiation of an IJP. NO-GC in SMC appears to enhance the nitrergic IJP, resulting in a stronger and prolonged hyperpolarization in fundus and colon SMC, respectively. Thus NO-GC in both cell types is mandatory to induce a full nitrergic IJP. Our data from the colon clearly reveal the nitrergic IJP to be biphasic, resulting from individual inputs of ICC and SMC.