Functional diversity of synaptic AMPA/KA receptors from rat as revealed by subtype-specific antagonists

Abstract

Subtype-specific pharmacological compounds represent important tools to identify the molecular components of synaptically activated glutamate receptors in central neurones. Here, we utilized a collection of subtype-specific antagonists and modulators to investigate the functional profile of glutamate receptors in identified synapses in thin slices of the cerebellum, hippocampus and brain stem. During whole-cell patch-clamp recordings alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate (AMPA/KA) receptor-mediated synaptic currents (EPSCs) in cerebellar Purkinje cells were (i) prolonged by 100 microM cyclothiazide, (ii) not significantly changed after preincubation in 10 microM concanavalin A, (iii) not affected by 1 microM Evans Blue or polyamine toxin analogue N-(4-hydroxyphenylpropanolyl)-spermine (NHPPS), but (iv) significantly reduced by high (> or = 100 microM) concentrations of Evans Blue. These pharmacological properties were distinct from those observed in hippocampal granule cells and brain stem interneurones and markedly different from those of recombinant glutamate receptor channels GluR1-GluR6 previously investigated in heterologous expression systems.