GABA(A) receptor delta subunit deletion prevents neurosteroid modulation of inhibitory synaptic currents in cerebellar neurons.
GABA(A) receptor delta subunit deletion prevents neurosteroid modulation of inhibitory synaptic currents in cerebellar neurons.
复制标题
GABA(A) 受体 δ 亚基缺失可防止神经类固醇对小脑神经元抑制性突触电流的调节。
DOI：
10.1016/s0028-3908(02)00126-0
复制
发表时间：
2002
影响因子：
4.7
通讯作者：
Homanics,GreggE
中科院分区：
文献类型：
--
作者：
Vicini,Stefano;Losi,Gabriele;Homanics,GreggE
GABAA受体的δ亚基在神经甾体调节中起关键作用。我们研究了神经甾体THDOC对δ亚基敲除小鼠小脑神经元GABA A受体介导的自发抑制性突触后电流（sIPSC）的作用。我们观察到，神经类固醇未能延长这些小鼠小脑切片中颗粒神经元的IPSC。这与在野生型小鼠中观察到的强增强相反。然而，在天然缺乏δ亚基的星状神经元中，在缺乏δ亚基的小鼠中也观察到在河豚毒素（mIPSC）存在下记录的神经类固醇对sIPSC的作用的显著减少。考虑到细胞内蛋白激酶C调节神经类固醇活性的作用，我们通过记录来自δ缺陷小鼠的sIPSC和mIPSC并在细胞内灌注激酶刺激剂来研究THDOC的作用。佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）完全恢复了神经甾体对颗粒和星状神经元突触电流的作用。
The δ subunit of the GABAAreceptor has been reported to play a pivotal role in neurosteroid modulation. We investigated the action of the neurosteroid THDOC on GABAAreceptor–mediated spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in cerebellar neurons from δ subunit knockout mice. We observed that the neurosteroid failed to prolong IPSCs in granule neurons in cerebellar slices from these mice. This was in contrast to robust potentiation observed in wild-type mice. However, in stellate neurons, naturally devoid of δ subunit, a significant reduction of neurosteroid action on sIPSCs recorded in the presence of tetrodotoxin (mIPSCs) was also observed in mice that lack the δ subunit. Given the reported role of intracellular protein kinase C modulation of neurosteroid activity, we investigated the action of THDOC by recording sIPSCs and mIPSCs from δ-deficient mice with intracellular perfusion of a kinase stimulator. Phorbol-12-myristate-13-acetate (PMA) completely restored the action of the neurosteroid on synaptic currents in both granule and stellate neurons.