Glycine receptor alteration in the mutant mouse spastic.
Glycine receptor alteration in the mutant mouse spastic.
复制标题
突变小鼠痉挛中甘氨酸受体的改变。
作者：
White,WF;Heller,AH
突变mousespastic在3号染色体上携带单位点隐性突变1（参考文献2，3），其特征为过度兴奋、快速震颤、僵硬和延长翻正反射1。在肌肉或中枢神经系统（CNS）的初步组织学研究中未发现解剖学异常1。对肥胖小鼠的肌电研究表明，活动期间出现异常的电脉冲和异常的刻板反射4。增加γ-氨基丁酸（GABA）5或增强GABA突触作用6的药物可减轻痉挛症状，表明这些症状是由痉挛中枢神经系统兴奋性和抑制性影响失衡引起的。士的宁拮抗甘氨酸的突触作用7，并结合到具有突触后甘氨酸受体特征的膜位点8 -11。痉挛小鼠的行为和电生理异常在给予亚惊厥剂量士的宁的正常小鼠中重现4，表明痉挛症状可能是由于甘氨酸介导的抑制缺乏4。我们在这里描述的证据，支持这一假设：减少3 H-士的宁结合在膜组分制备痉挛相比，同窝对照小鼠。我们还证明了苯二氮卓类，可能是GABA，在pasticphenotype结合位点的参与。
The mutant mousespastic, which carries a single-locus, recessive mutation1on chromosome 3 (refs 2, 3), is characterized by hyperexcitability, rapid tremor, rigidity and prolonged righting reflexes1. No anatomical abnormalities have been found in preliminary histological studies of muscle or the central nervous system (CNS)1. Electromyographic studies inspasticmice demonstrate abnormal electrical bursts during activity and abnormal stereotyped reflexes4. Drugs which increaseγ-aminobutyric acid (GABA)5or enhance GABA synaptic action6reducespasticsymptoms, suggesting that they result from an imbalance in excitatory and inhibitory influences in thespasticCNS. Strychnine antagonizes the synaptic action of glycine7, and binds to a membrane site with the characteristics of the postsynaptic glycine receptor8–11. The behavioural and electrophysiological abnormalities ofspasticmice are reproduced in normal mice given subconvulsive doses of strychnine4, suggesting thatspasticsymptoms might result from a deficiency in glycine-mediated inhibition4. We describe here evidence that supports this hypothesis: a decrease in3H-strychnine binding in membrane fractions prepared fromspasticcompared with littermate control mice. We also demonstrate an involvement of the benzodiazepine, and possibly the GABA, binding site in thespasticphenotype.