Evidence for more than one type of non-NMDA receptor in outside-out patches from cerebellar granule cells of the rat.

1. Application of non-NMDA (non-N-methyl-D-aspartate) receptor agonists onto outside-out patches of cerebellar granule cells gave two characteristic types of response (in different patches) which we have referred to as 'high conductance' and 'low conductance' responses. At a qualitative level these patches could be readily distinguished by the size of the noise increase accompanying their membrane currents. 2. In high conductance patches both AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate gave discrete single-channel conductances (10-30 pS), while in low conductance patches, AMPA produced small discrete events (6-10 pS), and kainate opened channels with conductances too small to be directly resolved. All patches examined contained NMDA receptor channels with characteristic 50 and 40 pS conductance levels. 3. Despite the marked differences in single-channel conductances, kainate dose-response curves constructed for high and low conductance patches had similar EC50 values of approximately 150 microM. 4. Spectral analysis of low conductance kainate responses gave an estimated channel conductance of approximately 1.5 pS. In these same low conductance patches AMPA produced discrete openings with two conductance levels; their mean conductances (and relative proportions) were 6 (87%) and 10 pS (13%). 5. In high conductance patches, glutamate (10-30 microM), AMPA (3-10 microM), and kainate (10-30 microM), each activated non-NMDA channels with three multiple conductance levels. The amplitudes of these conductance levels (approximately 10, 20 and 30 pS) were similar for each of the agonists, and their relative proportions (i.e. areas in the amplitude histograms) were constant for all three agonists. In addition, the relative proportion of levels was constant between patches, and all three levels were invariably present. These observations are all consistent with the idea that the three multiple conductances originate from a single receptor channel, activated by AMPA, kainate and glutamate. 6. Non-NMDA single-channel current-voltage (I-V) plots showed outward rectification in high conductance patches. For all three multiple conductance levels the ratio of outward to inward single-channel slope conductance was 1.8 +/- 0.1 and this rectification remained present in symmetrical Na+ solutions. 7. In high conductance patches, the events produced by a rapid application of 20-50 microM glutamate were compared with those activated during steady-state application.(ABSTRACT TRUNCATED AT 400 WORDS)