Chavis P, Fagni L, Bockaert J, Lansman J B
CNRS UPR 9023, CCIPE, Montpellier, France.
Neuropharmacology. 1995 Aug;34(8):929-37. doi: 10.1016/0028-3908(95)00082-h.
We investigated the mechanisms by which metabotropic glutamate receptors (mGluRs) modulate specific Ca2+ channels in cerebellar granule cells. A large fraction of the current in granule cells is carried by L- and Q-type Ca2+ channels (about 26% each), whereas N- and P-type contribute proportionally less to the global current (9 and 15%, respectively). l-Aminocyclopentane-dicarboxylate (t-ACPD), (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (L-CCGI) and (S)-4-carboxy-3-hydroxyphenylglycine [(S)-4C3HPG], but not L(+)-2-amino-4-phosphonobutyrate (L-AP4) reduced the Ca2+ current amplitude. The t-ACPD-induced inhibition was fully antagonized by (+/-)-methyl-4-carboxyphenylglycine [(+/-)-MCPG] and blocked by pertussis toxin (PTX). These results are consistent with inhibitory response mediated by mGluR2/R3. The use of specific Ca2+ channel blockers provided evidence that mGluR2/R3 inhibited both L- and N-type Ca2+ currents. In PTX-treated cells, Glu or t-ACPD, but not L-CCGI or L-AP4, increased the Ca2+ current. Consistent with the activation of mGluR1, the antagonists (+)-MCPG and (S)-4C3HPG prevented the facilitation of Ca2+ current produced by t-ACPD. The mGluR1-activated facilitation was completely blocked by nimodipine, indicating that L-type Ca2+ currents were selectively potentiated.
我们研究了代谢型谷氨酸受体（mGluRs）调节小脑颗粒细胞中特定Ca2+通道的机制。颗粒细胞中很大一部分电流由L型和Q型Ca2+通道传导（各约占26%），而N型和P型对整体电流的贡献相对较小（分别为9%和15%）。L-氨基环戊烷二羧酸（t-ACPD）、（2S,3S,4S）-α-（羧基环丙基）-甘氨酸（L-CCGI）和（S）-4-羧基-3-羟基苯甘氨酸[（S）-4C3HPG]可降低Ca2+电流幅度，但L（+）-2-氨基-4-膦酸丁酸（L-AP4）则不能。t-ACPD诱导的抑制作用可被（+/-）-甲基-4-羧基苯甘氨酸[（+/-）-MCPG]完全拮抗，并被百日咳毒素（PTX）阻断。这些结果与mGluR2/R3介导的抑制反应一致。使用特定的Ca2+通道阻滞剂提供了证据，表明mGluR2/R3可抑制L型和N型Ca2+电流。在PTX处理的细胞中，谷氨酸或t-ACPD可增加Ca2+电流，但L-CCGI或L-AP4则不能。与mGluR1的激活一致，拮抗剂（+）-MCPG和（S）-4C3HPG可阻止t-ACPD对Ca2+电流的增强作用。mGluR1激活的增强作用可被尼莫地平完全阻断，表明L型Ca2+电流被选择性增强。
