Srinivasan Y, Elmer L, Davis J, Bennett V, Angelides K
Department of Physiology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030.
Nature. 1988 May 12;333(6169):177-80. doi: 10.1038/333177a0.
The segregation of voltage-dependent sodium channels to specialized regions of the neuron is crucial for propagation of an action potential. Studies of their lateral mobility indicate that sodium channels are freely mobile on the neuronal cell body but are immobile at the axon hillock, presynaptic terminal and at focal points along the axon. To elucidate the mechanisms that regulate sodium channel topography and mobility, we searched for specific proteins from the brain that associate with sodium channels. Here we show that sodium channels labelled with 3H-saxitoxin (STX) are precipitated in the presence of exogenous brain ankyrin by anti-ankyrin antibodies and that 125I-labelled ankyrin binds with high affinity to sodium channels reconstituted into lipid vesicles. The cytoplasmic domain of the erythrocyte anion transporter competes for the latter interaction. Neither the neuronal GABA (gamma-aminobutyric acid) receptor channel complex nor the dihydropyridine (DHP) receptor bind brain ankyrin. The results indicate that brain ankyrin links the voltage-dependent sodium channel to the underlying cytoskeleton and may help to maintain axolemmal membrane heterogeneity and control sodium channel mobility.
电压依赖性钠通道在神经元特定区域的分隔对于动作电位的传导至关重要。对其侧向移动性的研究表明，钠通道在神经元细胞体上可自由移动，但在轴丘、突触前末端以及沿轴突的焦点处则固定不动。为阐明调节钠通道拓扑结构和移动性的机制，我们从大脑中寻找与钠通道相关的特定蛋白质。在此我们表明，用³H-石房蛤毒素（STX）标记的钠通道在外源脑锚蛋白存在的情况下会被抗锚蛋白抗体沉淀，并且¹²⁵I标记的锚蛋白与重构到脂质囊泡中的钠通道具有高亲和力结合。红细胞阴离子转运体的胞质结构域可竞争后一种相互作用。神经元γ-氨基丁酸（GABA）受体通道复合物和二氢吡啶（DHP）受体均不结合脑锚蛋白。结果表明，脑锚蛋白将电压依赖性钠通道与潜在的细胞骨架相连，可能有助于维持轴膜的膜异质性并控制钠通道的移动性。
