Heterogeneity of homomeric GluR5 kainate receptor desensitization expressed in HEK293 cells

1. Kainate receptors with pharmacological properties similar to those of th e GluR5 subunit have been shown to modulate inhibitory synaptic transmissio n in the CA1 region of the hippocampus. The kinetic properties of currents gated by GluR5 receptors have not been examined in detail. Here we describe several biophysical features of recombinant GluR5 receptors expressed in H EK293 cells. 2. We found that homomeric GluR5 receptors can exhibit striking inter-cell variability in channel kinetics in response to the agonists kainate and glu tamate. Desensitization rates in response to kainate varied between individ ual cells by nearly 1000-fold (range, 1.5 ms to 1.5 s), while glutamate des ensitization rates differed by 9-fold (range, 1.0 to 9.0 ms). 3. The time course of recovery from desensitization in response to glutamat e also showed intercell variation. The majority of glutamate currents in Gl uR5-expressing cells recovered from desensitization with two widely separat ed exponential components: 50 +/- 10 ms and 5.1 +/- 1.0 s (contributing 37. 6% and 82.4% of the sum of the exponential fits, respectively). In contrast , currents with the fastest desensitization kinetics had a recovery time co urse of 4.8 +/- 0.3 s. 4. Kainate receptors in murine dorsal root ganglion neurons are likely to b e composed of homomeric GluR5 subunits. These receptor currents recovered f rom glutamate desensitization with a biexponential time course of 36 +/- 4 ms and 4.7 +/- 0.7 s. 5. These results suggest that aspects of GluR5 kainate receptor function ar e modulated by intracellular mechanism(s). At synapses such mechanisms coul d regulate the frequency-response relationship of synaptic kainate receptor s by altering their rate of entry into and recovery from desensitization.