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Involvement of Na+-leak Channel in Substance P-induced Depolarization of Pacemaking Activity in Interstitial Cells of Cajal

机译:Na +泄漏通道参与物质P诱导的Cajal间质细胞起搏活动的去极化作用

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Interstitial cells of Cajal (ICCs) are the pacemaking cells in the gastrointestinal muscles that generate the rhythmic oscillations in membrane potential known as slow waves. ICCs also mediate or transduce inputs from the enteric nervous system. Substance P (SubP) is a member of the family of mammalian tachykinin peptides that are predominantly released by enteric neurons. This study assessed the relationship of Nasup+/sup-leak channel (NALCN) in the SubP-induced depolarization in pacemaking activity in the gastrointestinal tract. The patch-clamp technique for whole-cell recording was used in cultured cluster and single ICCs. Electrophysiological and pharmacological properties of SubP in ICC pacemaking activity were similar to those of NALCN. Reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry all showed abundant and localized expression of NALCN messenger RNA and protein in mouse small intestine. NALCN is involved in the SubP-induced depolarization of intestinal pacemaking activity. The protein is a potential target for pharmacological treatment of motor disorders of the gut.
机译:Cajal的间质细胞(ICCs)是胃肠道肌肉中的起搏细胞,在膜电位中产生有节奏的振荡,称为慢波。 ICC还介导或转导来自肠神经系统的输入。 P物质(SubP)是主要由肠神经元释放的哺乳动物速激肽肽家族的成员。本研究评估了SubP诱导的去极化去极化胃肠道中Na + -泄漏通道(NALCN)的关系。用于全细胞记录的膜片钳技术用于培养的簇和单个ICC。 SubP在ICC起搏活动中的电生理和药理特性与NALCN相似。逆转录聚合酶链反应,蛋白质印迹和免疫组化都显示在小鼠小肠中NALCN信使RNA和蛋白质的大量和局部表达。 NALCN参与SubP诱导的肠道起搏活动的去极化。该蛋白质是肠道运动障碍药物治疗的潜在靶标。

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