Li Gang, Niu Li
Department of Chemistry and the Center for Neuroscience Research, State University of New York, Albany, New York 12222, USA.
J Biol Chem. 2004 Feb 6;279(6):3990-7. doi: 10.1074/jbc.M310410200. Epub 2003 Nov 10.
Opening of a ligand-gated ion channel is the step at which the binding of a neurotransmitter is transduced into the electrical signal by allowing ions to flow through the transmembrane channel, thereby altering the postsynaptic membrane potential. We report the kinetics for the opening of the GluR1Qflip channel, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit of the ionotropic glutamate receptors. Using a laser-pulse photolysis technique that 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, after the binding of glutamate, the channel opened with a rate constant of (2.9 +/- 0.2) x 10(4) s(-1) and closed with a rate constant of (2.1 +/- 0.1) x 10(3) s(-1). The observed shortest rise time (20-80% of the receptor current response), i.e. the fastest time by which the GluR1Qflip channel can open, was predicted to be 35 micros. This value is three times shorter than those previously reported. The minimal kinetic mechanism for channel opening consists of binding of two glutamate molecules, with the channel-opening probability being 0.93 +/- 0.10. These findings identify GluR1Qflip as one of the temporally efficient receptors that transduce the binding of chemical signals (i.e. glutamate) into an electrical impulse.
神经递质的结合通过允许离子流过跨膜通道而转化为电信号，从而改变突触后膜电位。我们报告了离子型谷氨酸受体的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基GluR1Qflip通道开放的动力学。使用激光脉冲光解技术，该技术允许谷氨酸以约30微秒的时间常数从γ-O-(α-羧基-2-硝基苄基)谷氨酸（笼形谷氨酸）光解释放，我们发现，在谷氨酸结合后，通道以(2.9±0.2)×10⁴ s⁻¹的速率常数开放，以(2.1±0.1)×10³ s⁻¹的速率常数关闭。观察到的最短上升时间（受体电流响应的20%-80%），即GluR1Qflip通道能够开放的最快时间，预计为35微秒。该值比先前报道的值短三倍。通道开放的最小动力学机制包括两个谷氨酸分子的结合，通道开放概率为0.93±0.10。这些发现确定GluR1Qflip是将化学信号（即谷氨酸）的结合转化为电冲动的时间高效受体之一。
