Concanavalin A selectively reduces desensitization of mammalian neuronal quisqualate receptors (excitatory amino acid receptors/hippocampus/lectins/celi culture/voltage clamp)

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-a-amino-3-hydroxy-5-methyl-4-isoxazolepropri- onic acid (AMPA; a potent quisqualate-like agonist) showed rapid desensitization: at 100 ,AM 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 jAM, when recorded in Mg-free solution with 0.3 j,M 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 desen- sitization 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 desen- sitization 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 jAM, 250 s) but at steady state Con A increased the plateau current evoked by 100 jIM quisqualate to 13 times control. Succinyl-Con A produced only a small reduction of desensiti- zation to quisqualate, =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 neu- rons, 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.