Recruitment of functional GABA(A) receptors to postsynaptic domains by insulin
Recruitment of functional GABA(A) receptors to postsynaptic domains by insulin
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作者：
Wan, Q;Xiong, ZG;Wang, YT
哺乳动物中枢神经系统（CNS）中突触强度的改变发生在突触前和突触后位点（1，2）。然而，由于突触后受体可能被释放的递质饱和，增加活跃的突触后受体的数量可能是加强突触功效的更有效的方法（3-7）。但是没有证据表明神经递质受体能迅速聚集到CNS的突触后膜上。在此，我们报道了胰岛素引起A型γ-氨基丁酸（GABA（A））受体（CNS 8中介导突触抑制的主要受体）从转染的HEK 293细胞的细胞内室迅速移位到质膜，并且这种重新定位需要GABA（A）受体的β 2亚基。在CNS神经元中，胰岛素增加突触后膜和树突膜上GABA（A）受体的表达。我们发现胰岛素增加了功能性突触后GABA（A）受体的数量，从而增加了GABA（A）受体介导的微小抑制性突触后电流（mIPSC）的振幅，而不改变其时程。这些结果为突触后质膜的功能受体的快速募集提供了证据，提示了突触可塑性产生的基本机制。
Modification of synaptic strength in the mammalian central nervous system (CNS) occurs at both pre- and postsynaptic sites(1,2). However, because postsynaptic receptors are likely to be saturated by released transmitter, an increase in the number of active postsynaptic receptors may be a more efficient way of strengthening synaptic efficacy(3-7). But there has been no evidence for a rapid recruitment of neurotransmitter receptors to the postsynaptic membrane in the CNS, Here we report that insulin causes the type A gamma-aminobutyric acid (GABA(A)) receptor, the principal receptor that mediates synaptic inhibition in the CNS8, to translocate rapidly from the intracellular compartment to the plasma membrane in transfected HEK 293 cells, and that this relocation requires the beta 2 subunit of the GABA(A) receptor. In CNS neurons, insulin increases the expression of GABA(A) receptors on the postsynaptic and dendritic membranes. We found that insulin increases the number of functional postsynaptic GABA(A) receptors, thereby increasing the amplitude of the GABA(A)-receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) without altering their time course. These results provide evidence for a rapid recruitment of functional receptors to the postsynaptic plasmamembrane, suggesting a fundamental mechanism for the generation of synaptic plasticity.