Cardiff School of Biosciences, Cardiff University, Cardiff CF10 AX, United Kingdom.
J Neurosci. 2013 Feb 27;33(9):3780-5. doi: 10.1523/JNEUROSCI.4989-12.2013.
Tonic inhibitory GABA(A) receptor-mediated currents are observed in numerous cell types in the CNS, including thalamocortical neurons of the ventrobasal thalamus, dentate gyrus granule cells, and cerebellar granule cells. Here we show that in rat brain slices, activation of postsynaptic GABA(B) receptors enhances the magnitude of the tonic GABA(A) current recorded in these cell types via a pathway involving G G proteins, adenylate cyclase, and cAMP-dependent protein kinase. Using a combination of pharmacology and knockout mice, we show that this pathway is independent of potassium channels or GABA transporters. Furthermore, the enhancement in tonic current is sufficient to significantly alter the excitability of thalamocortical neurons. These results demonstrate for the first time a postsynaptic crosstalk between GABA(B) and GABA(A) receptors.
在中枢神经系统的许多细胞类型中都观察到紧张性抑制性 GABA(A) 受体介导的电流，包括腹侧基底丘脑的丘脑皮质神经元、齿状回颗粒细胞和小脑颗粒细胞。在这里，我们表明，在大鼠脑切片中，通过涉及 G 蛋白、腺苷酸环化酶和 cAMP 依赖性蛋白激酶的途径，激活突触后 GABA(B) 受体可增强这些细胞类型中记录到的紧张性 GABA(A) 电流的幅度。我们使用药理学和基因敲除小鼠的组合表明，该途径与钾通道或 GABA 转运体无关。此外，紧张性电流的增强足以显著改变丘脑皮质神经元的兴奋性。这些结果首次证明了 GABA(B) 和 GABA(A) 受体之间的突触后串扰。
