How Fast Does the GluR1Qflip Channel Open?

Abstract

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.