Rapid use‐dependent down‐regulation of γ‐aminobutyric acid type A receptors in rat mesencephalic trigeminal neurons
Rapid use‐dependent down‐regulation of γ‐aminobutyric acid type A receptors in rat mesencephalic trigeminal neurons
复制标题
大鼠中脑三叉神经元中γ-氨基丁酸A型受体的快速使用依赖性下调
DOI：
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发表时间：
2009
影响因子：
4.2
通讯作者：
Youngnam Kang
中科院分区：
文献类型：
--
作者：
M. Saito;H. Toyoda;Hajime Sato;H. Ishii;Youngnam Kang
Rundown是一种通过各种机制对受体或离子通道重复激活的响应，是一种使用依赖性下调。与AMPA受体相反，γ-氨基丁酸A型受体（GABAAR）被认为不显示快速的使用依赖性下调。我们在这里报告了大鼠中脑三叉神经核（MTN）初级感觉神经元中GABAAR的快速使用依赖性下调，该神经元除了表达突触外的GABAAR外，还表达突触GABAAR，与其他初级感觉神经元不同。在蝇蕈醇浴应用之前、期间和之后每2分钟将蝇蕈醇重复喷施于MTN神经元5分钟时，在电流钳和电压钳条件下获得的GABAA反应在浴应用期间几乎完全被抑制。然而，在浴用蝇蕈醇洗脱后15分钟，前者和后者GABAA反应分别恢复至其对照振幅的26% ± 7%和36% ± 7%。相比之下，当在白屈菜红碱（一种蛋白激酶C（PKC）抑制剂）的存在下连同细胞内Ca 2+的严格螯合一起检查时，抽吸响应几乎完全恢复，而单独使用白屈菜红碱或EGTA时，这些响应恢复到对照的40-60%。磷脂酰肌醇3激酶抑制剂（PI 3 K）渥曼青霉素（wortmannin）可阻断各种信号转导，包括囊泡运输，显著增强每2分钟检查一次的抽吸反应的下降。这些发现表明，MTN神经元中GABAA反应的下降是由GABAAR的使用依赖性下调介导的，这可通过PKC抑制和细胞内Ca 2+螯合作用逆转，同时通过PI 3 K抑制促进。© 2009 Wiley利斯公司
Rundown is ubiquitously seen in response to repetitive activation of receptor or ion channels as a use‐dependent down‐regulation through various mechanisms. In contrast to AMPA receptors, γ‐aminobutyric acid type A receptor (GABAAR) are believed to display no rapid use‐dependent down‐regulation. We report here a rapid use‐dependent down‐regulation of GABAAR in primary sensory neurons of rat mesencephalic trigeminal nucleus (MTN), which express synaptic GABAARs in addition to extrasynaptic ones, unlike other primary sensory neurons. When muscimol was repetitively puff‐applied to an MTN neuron every 2 min before, during, and after the muscimol bath application for 5 min, both the GABAA responses obtained under both current‐ and voltage‐clamp conditions were almost completely depressed during the bath application. However, the former and latter GABAA responses recovered to 26% ± 7% and 36% ± 7% of their control amplitudes, respectively, 15 min after washout of the bath‐applied muscimol. By contrast, when examined in the presence of chelerythrine, a protein kinase C (PKC) inhibitor, together with a stringent chelation of intracellular Ca2+, the puff responses were almost completely recovered, whereas those were recovered to 40–60% of the control by either chelerythrine or EGTA alone. A phosphatidylinositol 3‐kinase inhibitor (PI3K), wortmannin, which blocks various signal transductions, including vesicular trafficking, significantly enhanced the rundown of the puff responses examined every 2 min. These findings indicate that the rundown of GABAA response in MTN neurons is mediated by the use‐dependent down‐regulation of GABAAR, which is reversed by PKC inhibition together with intracellular Ca2+ chelation, while being facilitated by PI3K inhibition. © 2009 Wiley‐Liss, Inc.
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DOI：
10.1016/s0021-9258(18)81855-5
发表时间：
1989-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
C. Felder;M. Blecher;P. Jose
通讯作者：
C. Felder;M. Blecher;P. Jose
影响因子：
3.6
作者：
N. Leidenheimer;S. McQuilkin;L. Hahner;P. Whiting;R. Harris
通讯作者：
N. Leidenheimer;S. McQuilkin;L. Hahner;P. Whiting;R. Harris
影响因子：
2.5
作者：
C. A. D. Negro;S. H. Chandler
通讯作者：
C. A. D. Negro;S. H. Chandler
全细胞记录过程中γ-氨基丁酸A受体功能的“衰退”：磷酸化的可能作用。
影响因子：
3.6
作者：
Gyenes,M;Farrant,M;Farb,DH
通讯作者：
Farb,DH
多巴胺通过二酰甘油和蛋白激酶 C 诱导视网膜水平细胞中的神经突回缩。
DOI：
10.1073/pnas.87.24.9693
发表时间：
1990
影响因子：
11.1
作者：
Rodrigues,PdosS;Dowling,JE
通讯作者：
Dowling,JE