Evidence for Ca2+-permeable AMPA receptors in the olfactory bulb

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ( AMPA) receptors (AMPARs), a subtype of glutamate receptor, contribute to olfactory processing in the olfactory bulb ( OB). These ion channels consist of various combinations of the subunits GluR1-GluR4, which bestow certain properties. For example, AMPARs that lack GluR2 are highly permeable to Ca2+ and generate inwardly rectifying currents. Because increased intracellular Ca2+ could trigger a host of Ca2+-dependent odor-encoding processes, we used whole cell recording as well as histological and immunocytochemical (ICC) techniques to investigate whether AMPARs on rat OB neurons flux Ca2+. Application of 1-naphthylacetyl spermine (NAS), a selective antagonist of Ca2+-permeable AMPARs (CP-AMPARs), inhibited AMPAR-mediated currents in subsets of interneurons and principal cells in cultures and slices. The addition of spermine to the electrode yielded inwardly rectifying current-voltage plots in some cells. In OB slices, olfactory nerve stimulation elicited excitatory responses in juxtaglomerular and mitral cells. Bath application of NAS with (D),(L)-2-amino-5-phosphonovaleric acid (AP5) to isolate AMPARs suppressed the amplitudes of these synaptic responses compared with responses obtained using AP5 alone. Co2+ staining, which involves the kainate-stimulated influx of Co2+ through CP-AMPARs, produced diverse patterns of labeling in cultures and slices as did ICC techniques used with a GluR2-selective antibody. These results suggest that subsets of OB neurons express CP-AMPARs, including functional CP-AMPARs at synapses. Ca2+ entry into cells via these receptors could influence odor encoding by modulating K+ channels, N-methyl-(D)-aspartate receptors, and Ca2+-binding proteins, or it could facilitate synaptic vesicle fusion.