Membrane potential and intracellular Ca2+ oscillations activated by mGluRs in hippocampal stratum oriens/alveus interneurons.

Membrane potential and intracellular Ca2+ oscillations activated by mGluRs in hippocampal stratum oriens/alveus interneurons.
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海马定向层/肺泡中间神经元中 mGluR 激活的膜电位和细胞内 Ca2+ 振荡。

DOI:
10.1152/jn.1999.81.1.371
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发表时间:
1999
影响因子:
2.5
通讯作者:
J. Lacaille
J. Lacaille
中科院分区:
医学3区
文献类型:
--
作者:
G. L. Woodhall;Christine E. Gee;Richard Robitaille;J. Lacaille

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代谢型谷氨酸受体(mGluRs)在海马中间神经元中不均匀表达,其信号传导级联反应在很大程度上仍不清楚。我们的特点是振荡反应激活的mGluR激动剂1 S,3R-1-氨基环戊烷-1,3-二羧酸(1 S,3R-ACPD)在海马中间神经元的定向层-肺泡(OA),同时全细胞电流钳记录和细胞内钙离子成像共聚焦显微镜。1 S,3R-ACPD可诱导细胞膜振荡去极化和胞内Ca ~(2+)升高,而河豚毒素可使其持续存在,并可被Ⅰ和Ⅱ类mGluRs(S)-α-甲基-4-羧基苯甘氨酸拮抗剂阻断。细胞外Cd ~(2+)和无Ca ~(2+)培养液均可阻断细胞膜去极化和细胞内Ca ~(2+)升高。因此,mGluR反应需要通过电压门控Ca 2+通道的Ca 2+内流。用毒胡萝卜素和ryanodine耗竭细胞内钙库也能拮抗1 S,3R-ACPD反应,表明细胞内钙库的Ca 2+释放也是必要的。这些数据表明,振荡响应所产生的组I/II mGluRs涉及耦合的Ca 2+进入通过电压门控Ca 2+通道和Ca 2+释放从内部存储。相比之下,1 S,3R-ACPD只引起较小的去极化和细胞内Ca 2+的上升,没有振荡,在其他海马interneurons位于或接近层陷窝-分子。因此,mGluR介导的振荡反应在某些中间神经元亚型中特异性表达。谷氨酸和Ca 2+信号通路在特定中间神经元中的这种异质性表达可能与它们对兴奋性毒性的选择性脆弱性有关。
Metabotropic glutamate receptors (mGluRs) are expressed heterogeneously in hippocampal interneurons, and their signal transduction cascades remain largely unclear. We characterized an oscillatory response activated by the mGluR agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) in hippocampal interneurons of stratum oriens-alveus (OA) with simultaneous whole cell current-clamp recordings and intracellular Ca2+ imaging with confocal microscopy. 1S,3R-ACPD induced oscillatory membrane depolarizations and rises in intracellular Ca2+ that persisted in tetrodotoxin and were blocked by the antagonist of group I and II mGluRs (S)-alpha-methyl-4-carboxyphenylglycine. Membrane depolarizations and intracellular Ca2+ rises were blocked by extracellular Cd2+ and in Ca2+-free medium. mGluR responses therefore required Ca2+ influx via voltage-gated Ca2+ channels. 1S, 3R-ACPD responses were also antagonized by depleting intracellular stores with thapsigargin and ryanodine, indicating that Ca2+ release from intracellular stores was also necessary. These data suggest that oscillatory responses generated by group I/II mGluRs involve a coupling of Ca2+ entry through voltage-gated Ca2+ channels and Ca2+ release from internal stores. In contrast, 1S,3R-ACPD evoked only smaller depolarizations and intracellular Ca2+ rises, with no oscillations, in other hippocampal interneurons located in or near stratum lacunosum-moleculare. Thus mGluR-mediated oscillatory responses are specifically expressed in certain interneuron subtypes. This heterogeneous expression of glutamate and Ca2+ signaling pathways in specific interneurons may be relevant to their selective vulnerability to excitotoxicity.
大鼠脑 G 蛋白偶联谷氨酸受体的克隆、表达和基因结构
DOI: 10.1126/science.1656524
发表时间: 1991-05-31
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: HAGEN, FS
DOI: 10.1016/0169-328x(94)90259-3
发表时间: 1994-02-01
期刊: MOLECULAR BRAIN RESEARCH
影响因子: --
作者:
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通讯作者: YOUNG, AB
DOI: 10.1113/jphysiol.1990.sp018310
发表时间: 1990-11-01
影响因子: 5.5
作者:
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