Kinetics of homomeric GluR6 glutamate receptor channels

We studied the kinetics of the unedited version of rat GluR6 glutamate (glu) receptor channels, GluR6Q, in outside-out patches using a system for submillisecond solution exchange. Half-maximum activation of the channels was reached with similar to 0.5 mM glu. The maximum slope of the double-logarithmic plot of the peak current versus glu was similar to 1.3, indicating that at least two binding steps are necessary to open the channels. Currents in response to a pulse of 10 mM glu had a short rise time (10-90% of peak current) of similar to 220 mu s at similar to 20 degrees C. The rise time increased with falling glu concentration, reaching similar to 6.0 ms with 10 mu M glu, In the continued presence of glu, the channels desensitized, and this desensitization can be described with a single time constant of similar to 7.0 ms for a pulse of 10 mM glu. The steady-state current in response to a long pulse of 10 mM glu was below 1/280th of the peak current, The time constant of desensitization was found to be independent of concentration between 30.0 and 0.3 mM glu, but to be increased for lower concentrations. After a short pulse of 1 ms duration and 10 or 0.3 mM glu, currents decayed with a time constant of similar to 2.5 ms, Recovery from desensitization after a pulse took similar to 5 s, and the half-time of recovery was similar to 2.2 s, Continuous application of low concentrations of glutamate reduced the peak currents in response to a pulse of 10 mM glu markedly, Fifty percent response reduction was observed in the continuous presence of similar to 0.3 mu M glu. Our results for homomeric GluR6 agree with a cyclical reaction scheme developed for completely desensitizing, glu-activated channels on crayfish muscles.