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首页> 外文期刊>The European Journal of Neuroscience >Identification and characterization of Cs~+-permeable K~+ channel current in mouse cerebellar Purkinje cells in lobules 9 and 10 evoked by molecular layer stimulation
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Identification and characterization of Cs~+-permeable K~+ channel current in mouse cerebellar Purkinje cells in lobules 9 and 10 evoked by molecular layer stimulation

机译:分子层刺激诱发的小鼠小脑浦肯野小叶9和10中Cs〜+渗透性K〜+通道电流的鉴定和表征

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The mouse cerebellum consists of 10 lobules, which are distinguishable by their anatomical and functional properties. However, the differences in the slow postsynaptic currents (sPSCs) of Purkinje cells between lobules have not been well studied. We recorded the sPSCs of lobules 3, 9 and 10 evoked by tetanic stimulation of the molecular layer in cerebellar slices, and found a novel outward sPSC mediated by the GABA_B receptor in loblues 9 and 10 but hardly at all in lobule 3. We showed that the lobule-specific difference is at least partly attributable to differences in the density of GABAergic neurons (higher in lobule 10 than in lobules 3 and 9), and the functional expression level of postsynaptic GABA_B receptor currents (larger in lobules 9 and 10 than in lobule 3). The G-protein-coupled inward rectifying K~+ channel (GIRK) is known to be activated by GABA_B receptors; however, the outward sPSC was not blocked by a GIRK blocker, was not sensitive to Cs~+ block, and was observed when Cs~+ was used as a charge carrier. These results suggest that a K~+ channel other than GIRK could be activated by GABA_B receptors. KCNK13 is a Cs~+-permeable K~+ channel that shows intense expression of mRNA in Purkinje cells. KCNK13 current was enhanced by co-expression of G_(beta gamma), subunits and was observed when Cs~+ was used as a charge carrier in heterologous expression systems, and the amino acids critical for these features were identified by mutagenesis. Taken together, these results show that KCNK13 is a legitimate candidate for the Cs~+-permeable K~+ channel activated by GABA_B receptors, presumably via G_(beta gamma) subunits in Purkinje cells.
机译:小鼠小脑由10个小叶组成,通过其解剖和功能特性可以区分。但是,尚未充分研究小叶之间浦肯野细胞的慢突触后突触电流(sPSCs)的差异。我们记录了小脑片上分子层的破伤性刺激引起的小叶3、9和10的sPSC,发现在蓝叶9和10中由GABA_B受体介导的新型向外sPSC,但在小叶3中几乎没有。小叶特异性差异至少部分归因于GABA能神经元密度的差异(小叶10中高于小叶3和9),以及突触后GABA_B受体电流的功能表达水平(小叶9和10中高于小叶)。小叶3)。已知G蛋白偶联的内向整流K +通道(GIRK)被GABA_B受体激活。但是,向外的sPSC未被GIRK阻滞剂阻滞,对Cs〜+阻滞不敏感,并且在将Cs〜+用作电荷载体时可以观察到。这些结果表明,GABA_B受体可以激活除GIRK以外的K〜+通道。 KCNK13是可透过Cs〜+的K〜+通道,显示浦肯野细胞中mRNA的强烈表达。 KCNK13电流通过G_βγ亚基的共表达而增强,并在异源表达系统中将Cs〜+用作电荷载体时观察到,并且通过诱变鉴定了对这些特征至关重要的氨基酸。综上所述,这些结果表明,KCNK13是由GABA_B受体激活的Cs〜+渗透性K〜+通道的合法候选者,推测是通过Purkinje细胞中的G_ββ亚基激活的。

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