Age- and sex-related characteristics of tonic GABA currents in the rat substantia nigra pars reticulata.
Age- and sex-related characteristics of tonic GABA currents in the rat substantia nigra pars reticulata.
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DOI：
10.1007/s11064-015-1523-3
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发表时间：
2015-04
影响因子：
4.4
通讯作者：
Galanopoulou, A. S.
中科院分区：
文献类型：
--
作者：
Chudomel, O.;Hasson, H.;Bojar, M.;Moshe, S. L.;Galanopoulou, A. S.
关键词：
以往的研究表明，GABA能药物的药理作用和大鼠黑质网状部（SNRA）前部的突触后阶段性GABA能抑制反应具有年龄和性别特异性。在这里，我们调查是否有年龄和性别相关的差异表达的δ GABAA受体（GABAAR）亚基和GABAAR介导的紧张性电流。我们用δ-特异性免疫化学和全细胞膜片钳技术研究了雄性和雌性出生后第5 -9天（PN 5 -9）、PN 11 -16和PN 25 -32天（PN 25 -32）大鼠SNRA中GABAAR介导的紧张电流。我们观察到年龄相关的下降，但没有性别特异性的变化，荷包牡丹碱（BIM）敏感的GABAAR紧张性电流密度，这与PN 15和30之间SNRA中δ亚基的下降相关。此外，我们发现蝇蕈醇（GABAAR激动剂;部分GABACR激动剂）、THIP（4，5，6，7-四氢异恶唑并（5，4-c）吡啶-3-醇：α4β3δ GABAAR激动剂和GABACR拮抗剂）和唑吡坦（α1-亚基选择性GABAAR激动剂）可以以年龄和性别依赖性方式对GABAAR紧张性电流进行修饰。我们建议，出现的GABAAR敏感的抗惊厥作用的大鼠SNRA在发展过程中可能取决于发展下降的紧张性GABA能抑制大鼠SNRA神经元的活动，虽然其他性别特异性因素也参与。
Previous studies have shown that the pharmacologic effects of GABAergic drugs and the postsynaptic phasic GABAAergic inhibitory responses in the anterior part of the rat substantia nigra pars reticulata (SNRA) are age- and sex-specific. Here, we investigate whether there are age- and sex-related differences in the expression of the δ GABAA receptor (GABAAR) subunit and GABAAR mediated tonic currents. We have used δ-specific immunochemistry and whole cell patch clamp to study GABAAR mediated tonic currents in the SNRA of male and female postnatal day (PN) PN5-9, PN11-16, and PN25-32 rats. We observed age-related decline, but no sex-specific changes, in bicuculline (BIM) sensitive GABAAR tonic current density, which correlated with the decline in δ subunit in the SNRA between PN15 and 30. Furthermore, we show that the GABAAR tonic currents can be modified by muscimol (GABAAR agonist; partial GABACR agonist), THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol: α4β3δ GABAARs agonist and GABACR antagonist), and zolpidem (α1-subunit selective GABAAR agonist) in age-and sex-dependent manner specific for each drug. We propose that the emergence of the GABAAR-sensitive anticonvulsant effects of the rat SNRA during development may depend upon the developmental decline in tonic GABAergic inhibition of the activity of rat SNRA neurons, although other sex-specific factors are also involved.
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DOI：
10.1073/pnas.96.22.12905
发表时间：
1999-10-26
影响因子：
11.1
作者：
Mihalek, RM;Banerjee, PK;Homanics, GE
通讯作者：
Homanics, GE
影响因子：
3.3
作者：
Chudomel, O.;Herman, H.;Galanopoulou, A. S.
通讯作者：
Galanopoulou, A. S.
影响因子：
5.3
作者：
Atherton, JF;Bevan, MD
通讯作者：
Bevan, MD
影响因子：
5.6
作者：
GARANT, DS;XU, SG;MOSHE, SL
通讯作者：
MOSHE, SL
影响因子：
4.7
作者：
Leao, RM;Mellor, JR;Randall, AD
通讯作者：
Randall, AD