Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons.
Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons.
复制标题
代谢型谷氨酸受体介导的急性分离新皮质神经元 L 型钙电流抑制。
DOI：
10.1152/jn.1992.68.3.833
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发表时间：
1992
影响因子：
2.5
通讯作者：
Crill,WE
中科院分区：
文献类型：
--
作者：
Sayer,RJ;Schwindt,PC;Crill,WE
1.本文研究了代谢型谷氨酸受体（mGluR）对大鼠背侧额顶叶新皮层锥体神经元全细胞Ca ~（2+）电流的影响。选择性mGluR激动剂cis-（+/-）-1-aminocyclopentane-1，3-dicarboxylic acid [trans-ACPD（100 microM）]在10- 21日龄大鼠的43个细胞中的40个细胞中抑制峰值高阈值Ca 2+电流21 +/- 1.7%（平均值+/- SE）。与先前对mGluR的研究结果一致，谷氨酸、使君子酸和鹅膏蕈氨酸[而不是α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）]降低了Ca 2+电流，并且该反应不被离子型谷氨酸受体拮抗剂6-氰基-7-硝基-喹喔啉-2，3-二酮（CNQX）和DL-2-氨基-5-膦酰基戊酸（APV）阻断。对Ca 2+电流抑制的EC 50为使君子酸29 nM，谷氨酸2.3 μ M，反式-ACPD 13 μ M。2. trans-ACPD对低阈值Ca ~（2+）电流无明显调制作用。由mGluR抑制的高阈值CA 2+电流的组成部分由药理学确定;响应不受ω-芋螺毒素GVIA的影响，但被二氢吡啶类Ca 2+拮抗剂硝苯地平堵塞。二氢吡啶类Ca 2+激动剂（+）-SDZ 202-79]延长的Ca 2+尾电流被mGluR刺激抑制，与峰电流平行。这些结果强烈表明，L-型钙通道的调制mGluR。3.在用100 μ M鸟苷5 '-（γ-硫代）三磷酸（GTP-γ-S）透析的神经元中，第一次应用trans-ACPD（6个细胞中的5个）引起了Ca 2+电流抑制，但随后的应用则没有。用2 mM鸟苷5 '-（β-硫代）二磷酸（GDP-β-S）透析的神经元中的反应显著小于对照组。结果与mGluR通过与G蛋白连接而发挥作用一致。4.当外部Ca 2+被Ba 2+取代时，对mGluR激动剂的反应较小，表明电流抑制的机制的某些部分是Ca 2+依赖性的。由于mGluR刺激磷酸肌醇周转和其他类型神经元中细胞内储存的Ca 2+释放，因此考虑了释放的Ca 2+介导Ca 2+通道失活的可能性。然而，通过强细胞内Ca 2+缓冲[20 mM双-（邻氨基苯氧基）-N，N，N '，N'-四乙酸（BAPTA）]、通过用100 μ M肌醇-1，4，5-三磷酸（IP 3）透析或通过外部应用1 μ M毒胡萝卜素，Ca 2+电流抑制不减弱。5.我们的结论是，在新皮层神经元中，mGluR的一个行动是抑制高阈值的Ca 2+电流的L-型Ca 2+通道进行的组件。（400字处截断摘要）
1. The effects of metabotropic glutamate receptor (mGluR) stimulation on whole-cell Ca2+ currents were studied in pyramidal neurons isolated from the dorsal frontoparietal neocortex of rat. The selective mGluR agonist cis-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid [trans-ACPD (100 microM)] suppressed the peak high-threshold Ca2+ current by 21 +/- 1.7% (mean +/- SE) in 40 of 43 cells from 10- to 21-day-old rats. Consistent with previous findings for mGluR, glutamate, quisqualate, and ibotenate [but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] reduced the Ca2+ currents, and the responses were not blocked by the ionotropic glutamate receptor antagonists 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonovaleric acid (APV). EC50S for Ca2+ current suppression were 29 nM for quisqualate, 2.3 microM for glutamate, and 13 microM for trans-ACPD. 2. The low-threshold Ca2+ current was not modulated by trans-ACPD. The component of the high-threshold CA2+ current suppressed by mGluR was determined by pharmacology; the responses were not affected by omega-conotoxin GVIA but were occluded by the dihydropyridine Ca2+ antagonist nifedipine. Ca2+ tail currents prolonged by the dihydropyridine Ca2+ agonist (+)-SDZ 202-79] were suppressed by mGluR stimulation in parallel with the peak current. These findings strongly suggest that L-type Ca2+ channels are modulated by mGluR. 3. In neurons dialyzed with 100 microM guanosine 5'-(gamma-thio)triphosphate (GTP-gamma-S), Ca2+ current suppression was elicited by the first application of trans-ACPD (in 5 of 6 cells), but not by subsequent applications. Responses in neurons dialyzed with 2 mM guanosine 5'-(beta-thio)diphosphate (GDP-beta-S) were significantly smaller than controls. The results are consistent with mGluR acting via linkage to a G protein. 4. The responses to mGluR agonists were smaller when the external Ca2+ was replaced by Ba2+, indicating that some part of the mechanism underlying the current suppression is Ca2+ dependent. Because mGluR stimulates phosphoinositide turnover and release of Ca2+ from intracellular stores in other types of neurons, the possibility of released Ca2+ mediating inactivation of Ca2+ channels was considered. However, the Ca2+ current suppression was not attenuated by strong intracellular Ca2+ buffering [20 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)], by dialysis with 100 microM inositol-1,4,5-triphosphate (IP3), or by external application of 1 microM thapsigargin. 5. We conclude that in neocortical neurons, one action of mGluR is to suppress the component of high-threshold Ca2+ current conducted by L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)