Liu Sumei, Qu Mei-Hua, Ren Wei, Hu Hong-Zhen, Gao Na, Wang Guo-Du, Wang Xi-Yu, Fei Guijun, Zuo Fei, Xia Yun, Wood Jackie D
Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
J Comp Neurol. 2008 Dec 20;511(6):847-62. doi: 10.1002/cne.21874.
The canonical transient receptor potential (TRPC) family of ion channels is implicated in many neuronal processes including calcium homeostasis, membrane excitability, synaptic transmission, and axon guidance. TRPC channels are postulated to be important in the functional neurobiology of the enteric nervous system (ENS); nevertheless, details for expression in the ENS are lacking. Reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry were used to study the expression and localization of TRPC channels. We found mRNA transcripts, protein on Western blots, and immunoreactivity (IR) for TRPC1/3/4/6 expressed in the small intestinal ENS of adult guinea pigs. TRPC1/3/4/6-IR was localized to distinct subpopulations of enteric neurons and was differentially distributed between the myenteric and submucosal divisions of the ENS. TRPC1-IR was widely distributed and localized to neurons with cholinergic, calretinin, and nitrergic neuronal immunochemical codes in the myenteric plexus. It was localized to both cholinergic and noncholinergic secretomotor neurons in the submucosal plexus. TRPC3-IR was found only in the submucosal plexus and was expressed exclusively by neuropeptide Y-IR neurons. TRPC4/6-IR was expressed in only a small population of myenteric neurons, but was abundantly expressed in the submucosal plexus. TRPC4/6-IR was coexpressed with both cholinergic and nitrergic neurochemical codes in the myenteric plexus. In the submucosal plexus, TRPC4/6-IR was expressed exclusively in noncholinergic secretomotor neurons. No TRPC1/3/4/6-IR was found in calbindin-IR neurons. TRPC3/4/6-IR was widely expressed along varicose nerve fibers and colocalized with synaptophysin-IR at putative neurotransmitter release sites. Our results suggest important roles for TRPC channels in ENS physiology and neuronal regulation of gut function.
离子通道的典型瞬时受体电位（TRPC）家族与许多神经元过程有关，包括钙稳态、膜兴奋性、突触传递和轴突导向。据推测，TRPC通道在肠神经系统（ENS）的功能性神经生物学中很重要；然而，关于其在ENS中的表达细节尚不清楚。采用逆转录聚合酶链反应、蛋白质免疫印迹法和免疫组织化学法研究TRPC通道的表达和定位。我们在成年豚鼠的小肠ENS中发现了TRPC1/3/4/6的mRNA转录本、蛋白质免疫印迹上的蛋白以及免疫反应性（IR）。TRPC1/3/4/6-IR定位于不同的肠神经元亚群，并且在ENS的肌间神经丛和黏膜下神经丛之间分布不同。TRPC1-IR分布广泛，定位于肌间神经丛中具有胆碱能、钙视网膜蛋白和一氧化氮能神经元免疫化学标记的神经元。它定位于黏膜下神经丛中的胆碱能和非胆碱能分泌运动神经元。TRPC3-IR仅在黏膜下神经丛中发现，并且仅由神经肽Y-IR神经元表达。TRPC4/6-IR仅在一小部分肌间神经元中表达，但在黏膜下神经丛中大量表达。TRPC4/6-IR在肌间神经丛中与胆碱能和一氧化氮能神经化学标记共表达。在黏膜下神经丛中，TRPC4/6-IR仅在非胆碱能分泌运动神经元中表达。在钙结合蛋白-IR神经元中未发现TRPC1/3/4/6-IR。TRPC3/4/6-IR沿曲张神经纤维广泛表达，并在假定的神经递质释放位点与突触素-IR共定位。我们的结果表明TRPC通道在ENS生理学和肠道功能的神经元调节中起重要作用。
