Role of the alpha subunit in the modulation of GABA(A) receptors by anabolic androgenic steroids.
Role of the alpha subunit in the modulation of GABA(A) receptors by anabolic androgenic steroids.
复制标题
α 亚基在合成代谢雄激素类固醇调节 GABA(A) 受体中的作用。
DOI：
10.1016/j.neuropharm.2005.03.017
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发表时间：
2005
影响因子：
4.7
通讯作者：
Henderson,LeslieP
中科院分区：
文献类型：
--
作者：
Yang,Paul;Jones,BrianL;Henderson,LeslieP
Neural transmission mediated by circuits expressing α2subunit-containing γ-aminobutyric acid type A (GABAA) receptors is critical for the expression of behaviors known to be altered by anabolic androgenic steroids (AAS). Here we show that micromolar concentrations of AAS, which reflect levels found in steroid abusers, induce positive modulation of currents from α2β3γ2Lrecombinant receptors elicited by pulses of GABA that mimic synaptic conditions in a manner that is mechanistically distinct from modulation induced at α1β3γ2Lreceptors. Specifically, at α2-containing receptors, the AAS, 17α-methyltestosterone (17α-MeT) enhanced peak current, slowed deactivation, diminished desensitization, and promoted entry of receptors into more distal states along the activation pathway. Analysis of GABAAreceptor-mediated synaptic currents in primary cortical neurons followed by single cell real-time RT-PCR demonstrated that 17α-MeT enhancement of synaptic currents is proportional to the ratio of α2to α1subunit mRNA. Finally, we show that the modulation elicited by AAS is not comparable to that produced by micromolar concentrations of other positive allosteric modulators at α2-containing receptors. In sum, these data indicate that AAS elicit effects on GABAAreceptor function that depend significantly on α subunit composition and that the mechanism of AAS modulation of GABAAreceptors is distinct from that of other positive allosteric modulators.
