ACTIVATION AND DESENSITIZATION PROPERTIES OF NATIVE AND RECOMBINANT KAINATE RECEPTORS

The activation-inactivation properties of membrane currents induced by the rapid application of glutamate or kainate were studied in culture d hippocampal neurons and in HEK cells transfected with a cDNA encodin g the GluR6 subunit. The onset of desensitization was rapid and simila r in native and recombinant channels (similar to 80 s(-1) of onset rat e constant). Recovery from desensitization was slow and agonist-depend ent in neurons, proceeding slightly faster in GluR6 receptors. Half-ma ximal activation (EC50) of native channels was obtained at a glutamate concentration of 330 mu M, while the half-maximal steady state desens itization (IC1/2) was attained at 2.8 mu M. These values differed from those obtained in recombinant receptors (EC50 = 762 mu M and IC1/2 = 0.44 mu M). A small window under the crossing point of activation and inactivation curves was observed, indicating that, for some concentrat ions of either agonist, steady state channel activity could exist. In native receptors, this window presented maximum values at approximatel y 100 mu M for glutamate, which predicted well the potency of glutamat e to reduce the GABAergic drive in hippocampal slices. These data indi cate that for neuronal kainate receptors, the concentrations for half activation and half inactivation differ by two orders of magnitude suc h that the maximum response to a maintained concentration of glutamate is small, and the steady state dose response curve is skewed and bell shaped. (C) 1998 Elsevier Science Ltd. All rights reserved.