Hirono M, Konishi S, Yoshioka T
Department of Molecular Neurobiology, School of Human Sciences, Waseda University, Tokorozawa, 359, Japan.
Biochem Biophys Res Commun. 1998 Oct 29;251(3):753-8. doi: 10.1006/bbrc.1998.9465.
The mGluR agonist 1S,3R-ACPD induces a potent excitatory inward current in various central neurons, but the underlying mechanism is not fully understood. Thus, we explored the signal transduction mechanism underlying the 1S,3R-ACPD-induced inward current in mouse cerebellar Purkinje cells. Iontophoretic application of 1S,3R-ACPD produced a group I mGluR antagonist-sensitive inward current. This current closely resembled a slow synaptic inward current evoked by repetitive stimulation of parallel fibers. Although phosphoinositide hydrolysis is shown to be coupled with group I mGluRs, we found that intracellular injections of various PLC inhibitors and an IP3 receptor antagonist heparin only partially inhibited the 1S, 3R-ACPD-induced current. Moreover, intracellular injection of the Ca2+ chelator BAPTA or a selective Na+/Ca2+ exchange inhibitor KB-R7943 affected slightly the inward current. In contrast, infusion of GDPbetaS and GTPgammaS markedly suppressed the 1S,3R-ACPD-induced current. These results suggest that activation of mGluR1 in mouse cerebellar Purkinje cells by 1S,3R-ACPD application or by repetitive stimulation of parallel fibres induces an inward current with a minor contribution from intracellular Ca2+ or Na+/Ca2+ exchange.
代谢型谷氨酸受体（mGluR）激动剂1S,3R-ACPD可在多种中枢神经元中诱导出强烈的兴奋性内向电流，但其潜在机制尚未完全明确。因此，我们探究了1S,3R-ACPD在小鼠小脑浦肯野细胞中诱导内向电流的信号转导机制。离子电泳施加1S,3R-ACPD可产生一种对I组mGluR拮抗剂敏感的内向电流。该电流与平行纤维重复刺激诱发的缓慢突触内向电流极为相似。尽管已表明磷酸肌醇水解与I组mGluRs相关联，但我们发现，细胞内注射各种磷脂酶C（PLC）抑制剂和肌醇三磷酸（IP3）受体拮抗剂肝素仅部分抑制了1S,3R-ACPD诱导的电流。此外，细胞内注射Ca2+螯合剂1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸（BAPTA）或选择性钠/钙交换抑制剂KB-R7943对内向电流的影响较小。相反，注入鸟苷二磷酸β-硫酯（GDPβS）和鸟苷三磷酸γ-硫酯（GTPγS）可显著抑制1S,3R-ACPD诱导的电流。这些结果表明，通过施加1S,3R-ACPD或平行纤维重复刺激激活小鼠小脑浦肯野细胞中的mGluR1会诱导出内向电流，而细胞内Ca2+或钠/钙交换的贡献较小。
