CONCENTRATION-JUMP ANALYSIS OF VOLTAGE-DEPENDENT CONDUCTANCES ACTIVATED BY GLUTAMATE AND KAINATE IN NEURONS OF THE AVIAN COCHLEAR NUCLEUS

We have examined the mechanisms underlying the voltage sensitivity of pha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors in voltag e-clamped outside-out patches and whole cells taken from the nucleus m agnocellularis of the chick. Responses to either glutamate or kainate had outwardly rectifying current-voltage relations. The rate and exten t of desensitization during prolonged exposure to agonist, and the rat e of deactivation after brief exposure to agonist, decreased at positi ve potentials, suggesting that a kinetic transition was sensitive to m embrane potential. Voltage dependence of the peak conductance and of t he deactivation kinetics persisted when desensitization was reduced wi th aniracetam or blocked with cyclothiazide. Furthermore, the rate of recovery from desensitization to glutamate was not voltage dependent. Upon reduction of extracellular divalent cation concentration, kainate -evoked currents increased but preserved rectifying current-voltage re lations. Rectification was strongest at lower kainate concentrations. Surprisingly, nonstationary variance analysis of desensitizing respons es to glutamate or of the current deactivation after kainate removal r evealed an increase in the mean single-channel conductance with more p ositive membrane potentials. These data indicate that the rectificatio n of the peak response to a high agonist concentration reflects an inc rease in channel conductance, whereas rectification of steady-state cu rrent is dominated by voltage-sensitive channel kinetics.