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发育中的肠神经系统中的离子通道表达。

Ion channel expression in the developing enteric nervous system.

作者信息

Hirst Caroline S, Foong Jaime P P, Stamp Lincon A, Fegan Emily, Dent Stephan, Cooper Edward C, Lomax Alan E, Anderson Colin R, Bornstein Joel C, Young Heather M, McKeown Sonja J

机构信息

Department of Anatomy & Neuroscience, University of Melbourne, Parkville, Victoria, Australia.

Department of Anatomy & Neuroscience, University of Melbourne, Parkville, Victoria, Australia; Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.

出版信息

PLoS One. 2015 Mar 23;10(3):e0123436. doi: 10.1371/journal.pone.0123436. eCollection 2015.

Abstract

The enteric nervous system arises from neural crest-derived cells (ENCCs) that migrate caudally along the embryonic gut. The expression of ion channels by ENCCs in embryonic mice was investigated using a PCR-based array, RT-PCR and immunohistochemistry. Many ion channels, including chloride, calcium, potassium and sodium channels were already expressed by ENCCs at E11.5. There was an increase in the expression of numerous ion channel genes between E11.5 and E14.5, which coincides with ENCC migration and the first extension of neurites by enteric neurons. Previous studies have shown that a variety of ion channels regulates neurite extension and migration of many cell types. Pharmacological inhibition of a range of chloride or calcium channels had no effect on ENCC migration in cultured explants or neuritogenesis in vitro. The non-selective potassium channel inhibitors, TEA and 4-AP, retarded ENCC migration and neuritogenesis, but only at concentrations that also resulted in cell death. In summary, a large range of ion channels is expressed while ENCCs are colonizing the gut, but we found no evidence that ENCC migration or neuritogenesis requires chloride, calcium or potassium channel activity. Many of the ion channels are likely to be involved in the development of electrical excitability of enteric neurons.

摘要

肠神经系统起源于神经嵴衍生细胞(ENCCs),这些细胞沿着胚胎肠道向尾端迁移。利用基于PCR的芯片、逆转录聚合酶链反应(RT-PCR)和免疫组织化学技术,对胚胎小鼠中ENCCs的离子通道表达进行了研究。在胚胎发育第11.5天(E11.5)时,许多离子通道,包括氯离子通道、钙离子通道、钾离子通道和钠离子通道就已在ENCCs中表达。在E11.5和E14.5之间,众多离子通道基因的表达有所增加,这与ENCC迁移以及肠神经元的神经突首次延伸相吻合。先前的研究表明,多种离子通道可调节多种细胞类型的神经突延伸和迁移。对一系列氯离子或钙离子通道进行药理抑制,对培养外植体中的ENCC迁移或体外神经突形成没有影响。非选择性钾离子通道抑制剂四乙铵(TEA)和4-氨基吡啶(4-AP)会延迟ENCC迁移和神经突形成,但仅在也会导致细胞死亡的浓度下才会如此。总之,在ENCCs定殖于肠道的过程中会表达大量离子通道,但我们没有发现证据表明ENCC迁移或神经突形成需要氯离子、钙离子或钾离子通道的活性。许多离子通道可能参与了肠神经元电兴奋性的发育。

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