Responses of Pyriform Cortex Neurons to Excitatory Amino Acids" Voltage Dependence, Conductance Changes, and Effects of Divalent Cations

1. The actions of ionophoretically appliedN-methyl aspartate (NMA), quisqualate, and kainate, thought to activate three different types of excitatory amino acid receptors, were studied on pyramidal neurons of the rat pyriform cortex, maintained in an isolated, submerged, and perfused brain slice. Intracellular recordings were made with either K acetate or CsCl electrodes. 2. In most neurons all three agonists elicited monophasic responses which could be evoked at 20-sec intervals. Some neurons showed biphasic responses, most commonly to kainate but, on occasion, also for quisqualate. The slower component appeared to be correlated with excitotoxicity and, consequently, was difficult to study. As a result the kainate responses studied were from neurons selected for having a single component. 3. In neurons selected for having a linear current-voltage relationship or neurons loaded with Cs to suppress K conductance and linearize the current-voltage relationship, the average changes in resistance recorded during ionophoretic responses at resting potential were as follows: NMA, 131.2 ± 6.7% of control; kainate, 104.7 ± 5.8% of control; and quisqualate, 92.8 ± 2.8% of control. The magnitude and direction of the conductance change were very reproducible in any one neuron, but especially for kainate some cells showed clear conductance increases, while others showed clear conductance decreases. 4. Using CsCl electrodes it was possible to reduce K+ conductance and depolarize the neurons over a wider range. By passing depolarizing current it was possible to reverse the responses. The response to all three agonists reversed at the same depolarized potential. This observation indicates that while there are differences in the ionic channels associated with the three agonists at resting potential, the channels have similar properties at more depolarized potentials. 5. Responses to all three agonists were influenced by the concentrations of divalent cations in the perfusion medium. The NMA responses were most sensitive to Mg, increasing in amplitude in the absence of Mg and being depressed by Mg elevation. All responses were sensitive to Ca, with discharges being greatly increased by low Ca and depressed by high Ca. The kainate response was most sensitive to Ca concentration changes. 6. Unlike reports from other preparations the apparent conductance decreases to NMA were not altered by the perfusion of solutions with either no added Mg or no added Ca. 7. The NMA response was very much reduced in either Co (1–2mM) or Zn (100–200µM). In contrast, the quisqualate response was relatively insensitive to Co but was consistently increased in the presence of Zn. The kainate response was not consistently affected by either, although there was some variation in individual experiments. 8. These results are consistent with the hypothesis that there are at least three distinct types of receptors for the excitatory amino acids in pyriform cortex and that these receptors are associated with three distinct ionic channels. The channels have many similar properties but possibly differ in divalent cation binding sites which regulate conductance to other ions.