调制的GABA (A)受体通道闸门由戊巴比妥。

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斯坦巴赫JH, G的样子

调制的GABA (A)受体通道闸门由戊巴比妥。

杂志。2001年12月15日,537 (Pt 3): 715 - 33所示。

PubMed ID

11744750 (在PubMed

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文摘

1。我们学习了渠道控制的动力学性质的重组α1β2γ2 l GABA (A)受体是暂时性的表示293年人类胚胎肾细胞,使用cell-attached,单通道膜片钳技术。GABA受体被激活,beta-alanine或piperidine-4-sulfonic酸(p4),戊巴比妥的影响(PB)单通道活动检查。2。在相对高浓度的兴奋剂,单通道活动发生在定义良好的集群。从全球来看,PB增加集群事件的平均开放时间,在不改变意味着关闭时间。的PB转移曲线相关的概率在集群(P (o))降低受体激动剂的浓度,这种转变可能占平均开放时间的变化。3所示。星团内closed-time直方图包含四个组件。这些closed-dwell组件的持续时间和相对频率不受40 microM PB的存在,在任何受体激动剂浓度。 The duration of one component was dependent upon the concentration of agonist used to activate the receptor. Accordingly, the inverse of the mean duration of this component will be called the effective opening rate. 4. The channel-opening rate constant (beta) was determined from the value of the effective opening rate at a saturating agonist concentration. beta was about 1900 s(-1) when the receptors were activated by GABA, 1500 s(-1) when activated by beta-alanine, and too low to be determined when P4S was administered. In the presence of 40 microM PB, beta was about 1500 s(-1) when the receptors were activated by GABA, 1400 s(-1) when activated by beta-alanine, and 50 s(-1) when activated by P4S. Hence, the potentiating effect of PB is not mediated by a change in beta. The concentration of agonist producing a half-maximal effective opening rate also remained unaffected in the presence of PB, indicating that receptor affinity for agonists is not influenced by PB. 5. The distributions of the intracluster open durations elicited by GABA could be described by the sum of three exponentials, with mean durations of about 0.4, 2.4 and 6.3 ms. The duration and relative frequency of the components did not change with GABA concentration (20 microM to 1 mM). In the presence of 40 microM PB, however, the mean duration of the longest of the open times increased (mean durations of about 0.4, 2.0 and 13 ms). The intracluster open durations elicited by beta-alanine could be described by the sum of two exponential components (1.1 and 3.5 ms). However, in the presence of 40 microM PB the open-time distribution contained three exponential components (0.2, 2 and 10 ms). Finally, openings elicited by P4S exhibited two components (0.3 and 0.9 ms). In the presence of 40 microM PB, three components could be distinguished (0.5, 2.5 and 13 ms). 6. These observations indicate that the potentiating effect of PB on GABA type A (GABA(A)) receptors reflects effects on the open state(s) of the receptors. In the case of receptors activated by GABA, the observations are consistent with the idea that the action is the result of PB stabilizing one of the open states. The actions on receptors activated by P4S or beta-alanine are also broadly consistent with this idea. However, the changes in open-time distributions caused by PB appear to be more complex. Possible explanations of the effects of PB on gating by different agonists are considered.

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药物靶点

药物	目标	类	生物	药理作用	行动
戊巴比妥	γ-氨基丁酸受体亚基alpha -	蛋白质	人类	是的	电位器	细节