Kinetics of homomeric GluR6 glutamate receptor channels

Abstract

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 approximately 0.5 microM glu. The maximum slope of the double-logarithmic plot of the peak current versus glu was approximately 1.3, indicating that at least two binding steps are necessary to open the channels. Currents in response to a pulse of 10 microM glu had a short rise time (10-90% of peak current) of approximately 220 microseconds at approximately 20 degrees C. The rise time increased with falling glu concentration, reaching approximately 6.0 ms with 10 microM glu. In the continued presence of glu, the channels desensitized, and this desensitization can be described with a single time constant of approximately 7.0 ms for a pulse of 10 microM glu. The steady-state current in response to a long pulse of 10 microM 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 microM glu, but to be increased for lower concentrations. After a short pulse of 1 ms duration and 10 or 0.3 microM glu, currents decayed with a time constant of approximately 2.5 ms. Recovery from desensitization after a pulse took approximately 5 s, and the half-time of recovery was approximately 2.2 s. Continuous application of low concentrations of glutamate reduced the peak currents in response to a pulse of 10 microM glu markedly. Fifty percent response reduction was observed in the continuous presence of approximately 0.3 microM glu. Our results for homomeric GluR6 agree with a cyclical reaction scheme developed for completely desensitizing, glu-activated channels on crayfish muscles.

Atypical Functional Properties of GluK3-Containing Kainate Receptors

“…Overall, the recovery time course of GluK3 receptors is slightly faster than the one of GluK2 (Fig. 2 B) (Heckmann et al, 1996;Bowie and Lange, 2002;Barberis et al, 2008). Second, the deactivation rate of GluK3 receptors measured with brief (0.5 ms) glutamate (30 mM) applications was very fast (Fig.…”

“…For GluK2 receptors, subsaturating concentrations of glutamate evoked currents that were slower than those evoked by saturating concentrations ( Fig. 1 B) (Heckmann et al, 1996;Bowie, 2002;Barberis et al, 2008). Rise times increased steadily when the glutamate concentration decreased (Fig.…”

“…To address the role of desensitization in determining glutamate sensitivity quantitatively, we constructed kinetic models of GluK2 and GluK3 based on previously published model architectures for AMPA/kainate receptors ( Fig. 3A) (Heckmann et al, 1996;Robert and Howe, 2003;Barberis et al, 2008). To constrain these models, we determined other important kinetic parameters, recovery from desensitization, deactivation after short agonist pulses, single channel conductance, and open probability at the peak P o,peak ( Fig.…”

Attenuated Plasticity of Postsynaptic Kainate Receptors in Hippocampal CA3 Pyramidal Neurons

“…Finally, the slow kinetics and reduced potentiation might, in part, be caused by a slower rate of recovery from desensitization of kainate receptors compared with AMPA receptors. Recombinant kainate receptors have a significantly slower reactivation time course than AMPA receptors (Lomeli et al, 1994;Heckmann et al, 1996;Swanson and Heinemann, 1998;Bowie and Lange, 2002), and this may play a role in shaping mossy fiber KA-EPSCs because kainate receptors with intermediate desensitized states have slowed kinetics (Bowie and Lange, 2002). Although we did not observe the Ͼ80% reduction in KA-EPSC amplitudes during 1 Hz stimulation predicted by this model, a clear attenuation in amplitudes was apparent during the higher-frequency trains, such that the potentiation at the end of the train stimuli was 141% (compared with 294% at the peak of facilitation) (Fig.…”

GluR6/KA2 Kainate Receptors Mediate Slow-Deactivating Currents

“…This property is believed to underlie the summation of excitatory inputs and to participate in the efficacy of spike transmission under repeated presynaptic activity (Castillo et al, 1997;Vignes and Collingridge, 1997;Mulle et al, 1998;Frerking and Ohliger-Frerking, 2002;Goldin et al, 2007;Yang et al, 2007). In contrast, recombinant KARs activated by exogenous glutamate pulses mediate currents decaying more than one order of magnitude faster than KAR-EPSCs (Heckmann et al, 1996;Swanson et al, 2002;Bowie et al, 2003). To explain the causes of the slow KAR-EPSC kinetics, it has been first hypothesized that KARs would be located extrasynaptically and activated by glutamate spillover.…”