Concanavalin A selectively reduces desensitization of mammalian neuronal quisqualate receptors

A fast perfusion system was used to apply excitatory amino acids to embryonic hippocampal neurons grown in dissociated culture and voltage clamped in the whole-cell recording configuration. Responses to quisqualic acid and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA; a potent quisqualate-like agonist) showed rapid desensitization: at 100 microM the peak inward current declined to a plateau response on average 0.2 times the peak response (mean time constant, 30 ms). Responses to L-aspartic acid and N-methyl-D-aspartic acid also showed desensitization: at 100 microM, when recorded in Mg-free solution with 0.3 microM glycine, the peak inward current declined to a plateau value 0.5 times the peak, but with a time constant of desensitization (average, 248 ms) one order of magnitude slower than desensitization of responses to quisqualate. Responses to kainate and domoate (agonists at kainic acid receptors) did not show appreciable desensitization. Responses to L-glutamate and 5-Br-willardine (a potent non-NMDA receptor agonist), recorded in glycine-free solution with 1 mM Mg to suppress N-methyl-D-aspartic acid receptor activity, showed similar rapid desensitization to AMPA and quisqualate, but occurred with less depression of the peak current. The lectin concanavalin A (Con A) reduced desensitization at quisqualate receptors, with no effect on responses to kainate or N-methyl-D-aspartic acid. The effect of Con A developed slowly (average time constant at 2.5 microM, 250 s) but at steady state Con A increased the plateau current evoked by 100 microM quisqualate to 13 times control. Succinyl-Con A produced only a small reduction of desensitization to quisqualate, approximately 10% of that produced by native Con A. Con A did not change the decay time constant of fast excitatory synaptic currents evoked by stimulation of presynaptic neurons, although the peak synaptic current decreased after treatment with lectin. Con A was also without effect on the block of responses to kainate produced by coapplication of quisqualate.