Quisqualate receptor desensitization: Characterization and identification of a physiological role in cultured postnatal rat hippocampal neurons

The quisqualate receptor, a class of glutamate receptors, participates in a number of normal and pathological processes in the vertebrate central nervous system (CNS). The regulation of these receptors, then, is likely to be important to the proper functioning of the vertebrate CNS. A potentially effective means for regulating quisqualate receptor activity is desensitization, especially given its rapidity and extent. For this reason, quisqualate receptor desensitization was characterized and a physiological role for desensitization was identified in cultured postnatal rat hippocampal neurons.; The pharmacological, kinetic, and ionic properties of the desensitizing quisqualate response were studied using the patch clamp technique. The agonist dependence, current-voltage relationship, and pharmacology of the desensitizing quisqualate current indicate that it is mediated by an ionotropic quisqualate receptor. The concentration dependence and voltage dependence of both the rate and percentage of desensitization suggest that desensitization is not caused by quisqualate acting as an open channel blocker. The ionic dependence of desensitization further suggests that this phenomenon does not reflect an open channel block by an ion.; The lectin wheat germ agglutinin (WGA) reversibly inhibits ionotropic quisqualate receptor desensitization by interacting with carbohydrate residues and without altering other electrophysiologically assayable properties of the quisqualate response. Thus, the single channel correlate of desensitization was determined by examining the effect of WGA on the burst duration and single channel conductance of quisqualate-gated channels. WGA increased the burst duration and had no effect on the single channel conductance. These results suggest that desensitization results from a decrease in the probability of quisqualate-gated channels being open.; The role of desensitization in regulating synaptic responses mediated by ionotropic quisqualate receptors was assessed by determining the effect of WGA on evoked excitatory postsynaptic currents (epscs) and spontaneous miniature epscs. WGA increased the amplitude of evoked epscs and decreased their rate of decay. Spontaneous mepscs were similarly affected by WGA. These findings suggest that desensitization regulates excitatory synaptic events.