Rajendra S, Lynch J W, Pierce K D, French C R, Barry P H, Schofield P R
School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
Neuron. 1995 Jan;14(1):169-75. doi: 10.1016/0896-6273(95)90251-1.
Agonist binding to the inhibitory glycine receptor (GlyR) initiates the opening of a chloride-selective channel that modulates the neuronal membrane potential. Point mutations of the GlyR, substituting Arg-271 with either Leu or Gln, have been shown to underlie the inherited neurological disorder startle disease (hyperekplexia). We show that these substitutions result in the redistribution of GlyR single-channel conductances to lower conductance levels. Additionally, the binding of the glycinergic agonists beta-alanine and taurine to mutated GlyRs does not initiate a chloride current, but instead competitively antagonizes currents activated by glycine. These findings are consistent with mutations of Arg-271 resulting in the uncoupling of the agonist binding process from the channel activation mechanism of the receptor.
激动剂与抑制性甘氨酸受体（GlyR）结合会引发氯离子选择性通道的开放，从而调节神经元膜电位。已表明，将甘氨酸受体的精氨酸271位点分别替换为亮氨酸或谷氨酰胺的点突变是遗传性神经系统疾病惊吓症（惊跳亢进）的病因。我们发现，这些替换会导致甘氨酸受体单通道电导重新分布至较低的电导水平。此外，甘氨酸能激动剂β-丙氨酸和牛磺酸与突变型甘氨酸受体的结合不会引发氯离子电流，反而会竞争性拮抗由甘氨酸激活的电流。这些发现与精氨酸271位点的突变导致受体激动剂结合过程与通道激活机制解偶联的观点一致。
