Roles of Na+/Ca2+ exchanger isoforms NCX1 and NCX2 in motility in mouse ileum
Roles of Na+/Ca2+ exchanger isoforms NCX1 and NCX2 in motility in mouse ileum
复制标题
DOI：
10.1007/s00210-016-1271-1
复制
发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
K. Nishiyama;Y. Azuma;Ai Morioka;Natsuho Yoshida;Midori Teramoto;Kohta Tanioka;S. Kita;S. Hayashi;H. Nakajima;T. Iwamoto;T. Takeuchi
中科院分区：
文献类型：
--
作者：
K. Nishiyama;Y. Azuma;Ai Morioka;Natsuho Yoshida;Midori Teramoto;Kohta Tanioka;S. Kita;S. Hayashi;H. Nakajima;T. Iwamoto;T. Takeuchi
Na+/Ca~(2+)交换器(NCX)是一种质膜转运体，参与调节多种组织细胞内的钙离子浓度。尽管NCX在心脏、脑和肾脏中的作用已被广泛研究，但NCX影响胃肠动力的生理作用尚不完全清楚。在本研究中，我们重点研究了NCX亚型NCX1和NCX2在胃肠道回肠运动中的作用。研究了野生型小鼠(WT)、NCX1杂合子敲除小鼠(NCX1 HET)、NCX2 HET和NCX1.3转基因小鼠(NCX1.3 TG)对电场刺激回肠纵行肌电刺激的反应。EFS引起的阶段性收缩在EFS期间持续，而紧张性收缩发生在EFS结束后。我们发现，与WT相比，NCX2 HET的时相收缩和紧张性收缩的幅度明显减小，而NCX1 HET的幅度则不明显。此外，与WT相比，乙酰胆碱(ACh)和P物质(SP)引起的NCX2 HET的收缩幅度较小，而NCX1 HET的收缩幅度不大。相反，NCX1.3Tg的时相收缩和紧张性收缩的幅度比WT大。与EFS相似，NCX1.3TG的ACh收缩幅度大于WT。综上所述，NCX1和NCX2在回肠运动中起重要作用，提示NCX1和NCX2通过调节平滑肌对ACh和SP的敏感性来调节回肠运动。
The Na+/Ca2+exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca2+concentrations in various tissues. The physiological roles by which NCX influences gastrointestinal motility are incompletely understood, although its role in the heart, brain, and kidney has been widely investigated. In this study, we focused on the functions of the NCX isoforms, NCX1 and NCX2, in the motility of the ileum in the gastrointestinal tract. We investigated the response to electric field stimulation (EFS) in the longitudinal smooth muscle of the ileum obtained from wild-type mice (WT), NCX1-heterozygote knockout mice (NCX1 HET), NCX2 HET and smooth muscle-specific NCX1.3 transgenic mice (NCX1.3 Tg). EFS induced a phasic contraction that persisted during EFS and a tonic contraction that occurred after the end of EFS. We found that the amplitudes of the phasic and tonic contractions were significantly smaller in NCX2 HET, but not in NCX1 HET, compared to WT. Moreover, the magnitudes of acetylcholine (ACh)- and substance P (SP)-induced contractions of NCX2 HET, but not of NCX1 HET, were smaller compared to WT. In contrast, the amplitudes of the phasic and tonic contractions were greater in NCX1.3 Tg compared to WT. Similar to EFS, the magnitude of ACh-induced contraction was greater in NCX1.3 Tg than in WT. Taken together, our findings indicated that NCX1 and NCX2 play important roles in ileal motility and suggest that NCX1 and NCX2 regulate the motility in the ileum by controlling the sensitivity of smooth muscles to ACh and SP.