Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance
Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance
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DOI：
10.1038/35051086
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发表时间：
2001-01-04
期刊：
影响因子：
64.8
通讯作者：
Farrant, M
中科院分区：
文献类型：
--
作者：
Brickley, SG;Revilla, V;Farrant, M
许多神经元接受连续的或“强直”的突触输入，这增加了它们的膜电导，从而改变了兴奋信号的时空整合（1-3）。在小脑颗粒细胞中，尽管抑制性突触电流的频率相对较低，但突触释放的GABA（γ -氨基丁酸）的溢出(4)会产生由GABA(a)受体介导的持续电导（5-7），这也会改变颗粒细胞的兴奋性(8)。在这里，我们发现在缺乏GABAA受体的α - 6和δ -亚基的颗粒细胞中不存在这种强直传导。由于“泄漏”电导的增加，这些颗粒细胞对兴奋性突触输入的反应保持不变，这是在静止状态下存在的，具有双孔域K（+）通道TASK-1的特性（参考文献9- 12）。我们的研究结果强调了由GABAA受体介导的强直抑制的重要性，GABAA受体的丧失会触发一种形式的稳态可塑性，导致维持正常神经元行为的电压无关的K（+）电导的大小发生变化。
Many neurons receive a continuous, or 'tonic', synaptic input, which increases their membrane conductance, and so modifies the spatial and temporal integration of excitatory signals(1-3). In cerebellar granule cells, although the frequency of inhibitory synaptic currents is relatively low, the spillover of synaptically released GABA (gamma -aminobutyric acid)(4) gives rise to a persistent conductance mediated by the GABA(A) receptor(5-7) that also modifies the excitability of granule cells(8). Here we show that this tonic conductance is absent in granule cells that lack the alpha6 and delta -subunits of the GABAA receptor. The response of these granule cells to excitatory synaptic input remains unaltered, owing to an increase in a 'leak' conductance, which is present at rest, with properties characteristic of the two-pore-domain K(+) channel TASK-1 (refs 9- 12). Our results highlight the importance of tonic inhibition mediated by GABAA receptors, loss of which triggers a form of homeostatic plasticity leading to a change in the magnitude of a voltage-independent K(+) conductance that maintains normal neuronal behaviour.