Lavoie A M, Tingey J J, Harrison N L, Pritchett D B, Twyman R E
Program in Neuroscience, University of Utah, Salt Lake City 84112, USA.
Biophys J. 1997 Nov;73(5):2518-26. doi: 10.1016/S0006-3495(97)78280-8.
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-micros 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 alpha1beta1gamma2- or alpha2beta1gamma2-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 alpha2beta1gamma2 receptors than for alpha1beta1gamma2 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.
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方面所起的作用尚不清楚。我们采用快速配体施加(100微秒溶液交换)来研究α亚基组成对GABA诱发的激活和失活速率的影响。将编码α1β1γ2-或α2β1γ2-亚基的人类cDNA转染至HEK 293细胞。相同亚基的不同转染之间通道动力学相似,并且在同一片膜上的几次GABA施加中具有可重复性。α2β1γ2受体的电流上升至峰值的速度至少是α1β1γ2受体的两倍(分别反映在10 - 90%上升时间为0.5毫秒和1.0毫秒),并且在饱和GABA施加后失活速度慢六至七倍(长时间常数分别为208毫秒和31毫秒)。因此,α亚基组成决定了GABA(A)受体通道的激活和失活动力学,因此可能会影响抑制性突触后电流的动力学和效能。