Vicini Stefano, Losi Gabriele, Homanics Gregg E
Georgetown University, School of Medicine Department of Physiology and Biophysics, 3900 Reservoir Road NW, 20007 Washington DC, USA.
Neuropharmacology. 2002 Sep;43(4):646-50. doi: 10.1016/s0028-3908(02)00126-0.
The delta subunit of the GABA(A) receptor has been reported to play a pivotal role in neurosteroid modulation. We investigated the action of the neurosteroid THDOC on GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in cerebellar neurons from delta 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 delta subunit, a significant reduction of neurosteroid action on sIPSCs recorded in the presence of tetrodotoxin (mIPSCs) was also observed in mice that lack the delta 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 delta-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.
据报道，γ-氨基丁酸A（GABA(A)）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四氢脱氧皮质酮（THDOC）对从小脑δ亚基基因敲除小鼠的小脑神经元记录的GABA(A)受体介导的自发性抑制性突触后电流（sIPSCs）的作用。我们观察到，该神经甾体未能延长这些小鼠小脑切片颗粒神经元中的抑制性突触后电流（IPSCs）。这与在野生型小鼠中观察到的强烈增强作用形成对比。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，在存在河豚毒素（mIPSCs）的情况下记录到的神经甾体对sIPSCs的作用也显著降低。鉴于细胞内蛋白激酶C调节神经甾体活性的报道作用，我们通过记录来自δ亚基缺陷小鼠的sIPSCs和mIPSCs，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神经元和星状神经元突触电流的作用。
