Desensitization of AMPA receptors on horizontal cells isolated from crucian carp retina.

In horizontal cells freshly dissociated from crucian carp (Carassius auratus) retina, we recorded the whole-cell responses to rapid application of glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate. Currents induced by glutamate and AMPA, but not by kainate, usually showed extremely rapid desensitization. 1-(4-aminophenyl)-3-methylcarbamyl- 4-methyl-7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine (GYKI 53655), a selective AMPA receptor antagonist, was found to completely block glutamate- and kainate-induced currents, which were supposed to be mediated by activation of AMPA receptors. We further extensively studied the kinetics of desensitization of glutamate- and AMPA-induced currents in horizontal cells. The time constants for decay of whole-cell currents induced by glutamate and AMPA were 1.9 and 1.4 ms, respectively, and the equilibrium responses to glutamate and AMPA at concentrations over 1 mM were invariably less than 10% of the corresponding peak responses. We have determined the values of EC50 for glutamate and AMPA as 1.08 and 1.05 mM, respectively, which are nearly 100-fold higher than that reported previously. Dose dependence of desensitization was also investigated and the glutamate concentration for a half desensitization was 26 microM, much lower than the EC50. Furthermore, kainate and AMPA interacted at AMPA receptors of horizontal cells in a dual competitive manner: the response to kainate of low concentration (10 microM) was potentiated by the addition of 300 microM AMPA, while the responses induced by kainate of relatively higher doses (300 microM or more) were reduced. We conclude that crucian carp horizontal cells may exclusively express the AMPA subtype of glutamate receptors, which is characterized by extremely rapid desensitization.