Heterotrimeric guanosine triphosphate-binding protein-coupled modulatory actions of motilin on K+ channels and postsynaptic γ-aminobutyric acid receptors in mouse medial vestibular nuclear neurons.
Heterotrimeric guanosine triphosphate-binding protein-coupled modulatory actions of motilin on K+ channels and postsynaptic γ-aminobutyric acid receptors in mouse medial vestibular nuclear neurons.
复制标题
胃动素对小鼠内侧前庭核神经元 K+ 通道和突触后 γ-氨基丁酸受体的异三聚鸟苷三磷酸结合蛋白偶联调节作用。
DOI：
10.1111/ejn.12051
复制
发表时间：
2013
期刊：
影响因子：
3.4
通讯作者：
Todaka H
中科院分区：
文献类型：
--
作者：
Matsuzaki;F.;Shirane;M.;Matsumoto;M.;Nakayama;K. I.;Todaka H
一些中枢神经系统神经元表达胃肠激素受体，但其药理作用尚不清楚。先前的解剖学和单位记录研究表明，一组小脑浦肯野细胞表达胃动素受体，胃动素抑制前庭核神经元的棘波放电，直接接受小脑抑制在大鼠或兔。本文采用切片-贴片记录法研究了胃动素对小鼠前庭内侧核神经元（MVNs）的药理作用，MVNs在眼反射控制中起重要作用。用抗胃动素受体抗体标记少量MVN以及小脑絮状浦肯野细胞。在一组MVNs中，水浴应用胃动素（0.1 μm）以剂量依赖性方式降低自发动作电位放电频率（Kd，0.03 μm）。胃动素对自发动作电位的作用被apamin（100 nm）阻断，apamin是一种小电导Ca 2+激活的K+通道阻断剂。此外，胃动素增强抑制性突触后电流（IPSC）和微型IPSC的幅度，但不影响微型IPSC的频率。细胞内应用百日咳毒素（PTx）（0.5 μg/μL）或三磷酸鸟苷-γ-S（1 mm）可抑制胃动素对动作电位和IPSC的作用。在从野生型小鼠获得的切片上检查的MVNs中只有30%，但在从囊泡γ-氨基丁酸转运蛋白-Venus转基因小鼠获得的切片上研究的GABA能MVNs中没有一个显示出对动作电位和IPSC的胃动素反应。这些结果表明，胃动素可以通过异三聚体三磷酸鸟苷结合蛋白偶联受体调节一组多巴胺能MVNs的小电导钙激活的K+通道和突触后γ-氨基丁酸受体。
Some central nervous system neurons express receptors of gastrointestinal hormones, but their pharmacological actions are not well known. Previous anatomical and unit recording studies suggest that a group of cerebellar Purkinje cells express motilin receptors, and motilin depresses the spike discharges of vestibular nuclear neurons that receive direct cerebellar inhibition in rats or rabbits. Here, by the slice‐patch recording method, we examined the pharmacological actions of motilin on the mouse medial vestibular nuclear neurons (MVNs), which play an important role in the control of ocular reflexes. A small number of MVNs, as well as cerebellar floccular Purkinje cells, were labeled with an anti‐motilin receptor antibody. Bath application of motilin (0.1 μm) decreased the discharge frequency of spontaneous action potentials in a group of MVNs in a dose‐dependent manner (Kd, 0.03 μm). The motilin action on spontaneous action potentials was blocked by apamin (100 nm), a blocker of small‐conductance Ca2+‐activated K+channels. Furthermore, motilin enhanced the amplitudes of inhibitory postsynaptic currents (IPSCs) and miniature IPSCs, but did not affect the frequencies of miniature IPSCs. Intracellular application of pertussis toxin (PTx) (0.5 μg/μL) or guanosine triphosphate‐γ‐S (1 mm) depressed the motilin actions on both action potentials and IPSCs. Only 30% of MVNs examined on slices obtained from wild‐type mice, but none of the GABAergic MVNs that were studied on slices obtained from vesicular γ‐aminobutyric acid transporter‐Venus transgenic mice, showed such a motilin response on action potentials and IPSCs. These findings suggest that motilin could modulate small‐conductance Ca2+‐activated K+channels and postsynaptic γ‐aminobutyric acid receptors through heterotrimeric guanosine triphosphate‐binding protein‐coupled receptor in a group of glutamatergic MVNs.