Activation and deactivation rates of recombinant GABA(A) receptor channels are dependent on alpha-subunit isoform

Activation and deactivation rates of recombinant GABA(A) receptor channels are dependent on alpha-subunit isoform
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DOI:
10.1016/s0006-3495(97)78280-8
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发表时间:
1997-11-01
影响因子:
3.4
通讯作者:
Twyman, RE
Twyman, RE
中科院分区:
生物学3区
文献类型:
--
作者:
Lavoie, AM;Tingey, JJ;Twyman, RE

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亚基组成在决定GABA(A)受体通道的内在最大激活和失活动力学中的作用尚不清楚。我们使用快速配体的应用程序(100亩的溶液交换),以检查α-亚基组合物对GABA诱发的激活和失活率的影响。用编码α(1)β(1)γ(2)-或α(2)β(1)γ(2)-亚基的人cDNA转染HEK 293细胞。通道动力学在相同亚基的不同转染中是相似的,并且在相同贴片中的几种GABA应用中是可重复的。在饱和GABA应用后,α(2)β(1)γ(2)受体的电流上升到峰值的速度至少是α(1)β(1)γ(2)受体的两倍(反映在10-90%上升时间分别为0.5 ms和1.0 ms),失活慢6 - 7倍(长时间常数为208 ms和31 ms)。因此,α-亚基组成决定GABA(A)受体通道的激活和失活动力学,因此可能影响抑制性突触后电流的动力学和功效。
The role of subunit composition in determining intrinsic maximum activation and deactivation kinetics of GABA(A) receptor channels is unknown. We used rapid ligand application (100-mu s solution exchange) to examine the effects of alpha-subunit composition on GABA-evoked activation and deactivation rates. HEK 293 cells were transfected with human cDNAs encoding alpha(1) beta(1) gamma(2)- or alpha(2) beta(1) gamma(2)-subunits. Channel kinetics were similar across different transfections of the same subunits and reproducible across several GABA applications in the same patch. Current rise to peak was at least twice as fast for alpha(2) beta(1) gamma(2) receptors than for alpha(1) beta(1) gamma(2) receptors (reflected in 10-90% rise times of 0.5 versus 1.0 ms, respectively), and deactivation was six to seven times slower (long time constants of 208 ms versus 31 ms) after saturating GABA applications. Thus alpha-subunit composition determined activation and deactivation kinetics of GABA(A) receptor channels and is therefore likely to influence the kinetics and efficacy of inhibitory postsynaptic currents.