老年费希尔344大鼠基底前脑神经元中γ-氨基丁酸激活的膜电流增强。
Enhancement of GABA-activated membrane currents in aged Fischer 344 rat basal forebrain neurons.
作者信息
Griffith W H, Murchison D A
机构信息
Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University, College Station 77843.
出版信息
J Neurosci. 1995 Mar;15(3 Pt 2):2407-16. doi: 10.1523/JNEUROSCI.15-03-02407.1995.
Changes in GABAergic systems have been widely documented during development. Similar changes might also occur during aging, but little information is currently available. Whole-cell and single-channel GABAA-activated currents were studied in acutely dissociated basal forebrain neurons. An age-related increase in whole-cell GABA currents was observed in cells from aged (19-25 month) Fischer 344 rats. The GABA current from aged animals displayed a greater maximum response, with no change in EC50 or slope of the GABA response curve. A reduction in use-dependent slow receptor desensitization was also observed in aged cells. Single-channel conductance and channel open time were unchanged with age, suggesting no alteration in the properties of single GABA channels. The benzodiazepine, midazolam, potentiated GABA currents to a greater degree in aged animals, consistent with previous reports of enhanced benzodiazepine activity with age. Ontogeny of the GABAA receptor/ion channel complex may continue through the stages of development, maturation, and aging.
γ-氨基丁酸（GABA）能系统的变化在发育过程中已有广泛记载。类似的变化在衰老过程中可能也会发生，但目前相关信息较少。我们对急性分离的基底前脑神经元中的全细胞和单通道GABAA激活电流进行了研究。在老年（19 - 25月龄）的Fischer 344大鼠的细胞中观察到全细胞GABA电流随年龄增长而增加。老年动物的GABA电流表现出更大的最大反应，而GABA反应曲线的半数有效浓度（EC50）或斜率没有变化。在老年细胞中还观察到使用依赖性慢受体脱敏作用减弱。单通道电导和通道开放时间不会随年龄而改变，这表明单个GABA通道的特性没有变化。苯二氮䓬类药物咪达唑仑在老年动物中对GABA电流的增强作用更大，这与之前关于苯二氮䓬类药物活性随年龄增强的报道一致。GABAA受体/离子通道复合体的个体发生可能会贯穿发育、成熟和衰老阶段。
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