Characterisation of kainate receptor mediated whole-cell currents in rat cultured cerebellar granule cells

Whole-cell voltage clamp recordings have been used to identify and characte rise inward currents mediated by native kainate receptors in rat cultured c erebellar granule cells. While the selective AMPA receptor antagonist GYKI 53655 (50 mu M) completely abolished inward currents evoked by AMPA (10-100 mu M) in the presence of cyclothiazide (100 mu M), kainate evoked currents in cells pretreated with concanavalin A (Con A) always showed a component (35-140 pA, n = 13) resistant to blockade. The majority (73 +/- 7%, it = 5) of GYKI 53655-resistant kainate-evoked inward currents remained in the pre sence of 100 mu M AMPA. However, these currents were reversibly blocked by the competitive AMPA/kainate receptor antagonist NBQX (100 mu M). (2S, 4R)- 4-methylglutamate (SYM 2081, 10 mu M) evoked inward currents in Con A treat ed cells (15-60 pA, n = 7), which were resistant to complete blockade by GY KI 53655 (50 mu M) but antagonised by NBQX (100 mu M). Kainate-evoked respo nses in the presence of GYKI 53655 (50 mu M) had linear or slightly outward ly rectifying current-voltage (I-V) relationships in all cells examined (n = 5) and were resistant to blockade by Joro spider toxin (JsTx, 1 mu M; n = 5). These results provide evidence that rat cultured cerebellar granule ce lls express functional kainate receptors made up of subunits which are edit ed at the Q/R site, and that SYM 2081 is an agonist at these native kainate receptors with a greater selectivity than kainate itself. (C) 1999 Elsevie r Science Ltd. All rights reserved.