Li Gang, Pei Weimin, Niu Li
Department of Chemistry and Center for Neuroscience Research, University at Albany, State University of New York, Albany, New York 12222, USA.
Biochemistry. 2003 Oct 28;42(42):12358-66. doi: 10.1021/bi0347961.
AMPA receptors mediate fast excitatory neurotransmission in the central nervous system. GluR2 is an AMPA receptor subunit that controls some key heteromeric AMPA receptor properties, such as calcium permeability. The kinetic properties of GluR2, relevant to the time scale of its channel opening, however, are poorly understood. Here, to measure the channel-opening kinetics, we use a laser-pulse photolysis technique, which permits glutamate to be liberated photolytically from gamma-O-(alpha-carboxy-2-nitrobenzyl)glutamate (caged glutamate) with a time constant of approximately 30 micros. We show that GluR2Q(flip), an unedited and Ca(2+) permeable isoform, is by far the fastest ligand-gated channel with the channel-opening and -closing rate constants being (8.0 +/- 0.49) x 10(4) and (2.6 +/- 0.20) x 10(3) s(-1), respectively. Therefore, the shortest rise time (20-80% of the receptor current response) or the fastest observed time by which the GluR2Q(flip) channel can open is predicted to be 17 micros. The minimal kinetic mechanism for the channel opening is further consistent with the binding of two glutamate molecules with the channel-opening probability of 0.96. These results suggest that GluR2 is a temporally, highly efficient receptor to transduce the binding of chemical signals (i.e., glutamate) into an electrical impulse.
AMPA 受体介导中枢神经系统中的快速兴奋性神经传递。GluR2 是一种 AMPA 受体亚基，可控制一些关键的异聚 AMPA 受体特性，如钙通透性。然而，与 GluR2 通道开放时间尺度相关的动力学特性却知之甚少。在这里，为了测量通道开放动力学，我们使用了激光脉冲光解技术，该技术允许谷氨酸从 γ-O-(α-羧基-2-硝基苄基)谷氨酸（笼形谷氨酸）中通过光解释放出来，时间常数约为 30 微秒。我们发现，未编辑且 Ca(2+) 可通透的异构体 GluR2Q(flip) 是迄今为止最快的配体门控通道，其通道开放和关闭速率常数分别为(8.0 ± 0.49) x 10(4) 和(2.6 ± 0.20) x 10(3) s(-1)。因此，预计 GluR2Q(flip) 通道能够开放的最短上升时间（受体电流响应的 20 - 80%）或最快观察时间为 17 微秒。通道开放的最小动力学机制进一步与两个谷氨酸分子的结合以及 0.96 的通道开放概率相一致。这些结果表明，GluR2 是一种在时间上高效的受体，能够将化学信号（即谷氨酸）的结合转化为电冲动。
