Kirsch Joachim
Institute for Anatomy and Cell Biology, Department of Medical Cell Biology, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
Cell Tissue Res. 2006 Nov;326(2):535-40. doi: 10.1007/s00441-006-0261-x. Epub 2006 Jun 29.
Inhibition in the mature central nervous system is mediated by activation of gamma-aminobutyric acid (GABA(A)) and glycine receptors. Both receptors belong to the same superfamily of ligand-gated ion channels and share common transmembrane topology and structural and functional features. Glycine receptors are pentameric ligand-gated anion channels composed of two different subunits, named alpha und beta, that assemble with a fixed stoichiometric ratio of two alpha to three beta subunits. Four genes encoding the alpha subunits exist, whereas only one gene encoding the beta subunit has been detected. Ligand binding occurs at the interface of alpha and beta subunits. The beta subunit, which is unable to form homo-oligomeric receptors, is responsible for assembly and channel properties. Moreover, this subunit carries a binding motif for the cytoplasmic protein gephyrin, which is believed to mediate synaptic clustering and anchoring at inhibitory synapses by interacting with the subsynaptic cytoskeleton. Synaptic gephyrin appears to restrict the mobility of glycine receptors diffusing in the plane of the plasma membrane, thereby generating dynamic plasma membrane domains contributing to the plasticity of inhibitory synapses. Glycine receptors are well established as playing important roles in controlling motor functions and sensory signaling in vision and audition and those in the dorsal horn of the spinal cord are now considered to be new targets for pain therapies. Like GABA(A) receptors, glycine receptors have been shown to be depolarizing during development. The functional meaning of the developmental switch from excitatory to inhibitory glycine receptor action remains to be elucidated.
成熟中枢神经系统中的抑制作用是由γ-氨基丁酸（GABA(A)）受体和甘氨酸受体的激活介导的。这两种受体都属于配体门控离子通道的同一超家族，具有共同的跨膜拓扑结构以及结构和功能特征。甘氨酸受体是由两种不同亚基组成的五聚体配体门控阴离子通道，分别命名为α和β，它们以两个α亚基与三个β亚基的固定化学计量比组装而成。已发现有四个基因编码α亚基，而仅检测到一个编码β亚基的基因。配体结合发生在α亚基和β亚基的界面处。β亚基无法形成同聚体受体，它负责组装和通道特性。此外，该亚基带有细胞质蛋白gephyrin的结合基序，据信该基序通过与突触下细胞骨架相互作用来介导抑制性突触处的突触聚集和锚定。突触gephyrin似乎限制了甘氨酸受体在质膜平面内扩散的流动性，从而产生有助于抑制性突触可塑性的动态质膜结构域。甘氨酸受体在控制运动功能以及视觉和听觉中的感觉信号传导方面发挥重要作用，这一点已得到充分证实，并且脊髓背角中的甘氨酸受体现在被认为是疼痛治疗的新靶点。与GABA(A)受体一样，甘氨酸受体在发育过程中已被证明具有去极化作用。从兴奋性到抑制性甘氨酸受体作用的发育转变的功能意义仍有待阐明。
