![]() Multiple open levels in AMPA receptors were first observed in studies of cultured CNS neurons ( Cull-Candy and Usowicz, 1987 Jahr and Stevens, 1987 Ascher and Nowak, 1988 Cull-Candy et al., 1988). Studies of recombinant AMPA receptors have shown that homomeric, as well as heteromeric, channels display multiple conductance levels whose amplitudes depend on subunit composition ( Swanson et al., 1997 Rosenmund et al., 1998 Derkach et al., 1999). Because of the extensive array of potential AMPA receptor assemblies and neuron-to-neuron differences in subunit expression, it is not surprising that previous studies have found considerable variability in AMPA receptor phenotype ( McBain and Dingledine, 1993 Yamada and Tang, 1993 Geiger et al., 1995 Fleck et al., 1996 Tóth and McBain, 1998). AMPA receptors are multimeric assemblies of the glutamate receptor (GluR) subunits GluR1–4, and their subunit composition and stoichiometry, as well as RNA editing and alternative splicing, influence several important channel properties ( Hollmann and Heinemann, 1994 Bettler and Mulle, 1995 Dingledine et al., 1999). Our results suggest that granule cells express a heterogeneous population of AMPA receptors, a subset of which are segregated to postsynaptic sites after synaptogenesis.Īlthough AMPA receptors mediate EPSCs in most CNS neurons, the single-channel properties of these receptors have not been directly studied in neurons in situ. We did, however, detect AMPA receptors with apparent unitary conductances of <1 pS in patches from both migrating and mature granule cells. ![]() In contrast to patches from migrating granule cells, we rarely observed directly resolvable single-channel currents in patches excised from the somata of granule cells in the internal granular layer, even though these cells gave large AMPA receptor whole-cell currents. The conductance levels observed varied substantially for different channels, although on average the values fell within the range of unitary conductances estimated previously for synaptic AMPA receptors. Analysis of the single-channel activity in these patches showed that individual AMPA receptors exhibit as many as four distinguishable conductance levels. At saturating agonist concentrations, the open probability of channels in outside-out patches from migrating cells was very high, allowing us to identify patches that contained only one or two active channels. Using whole-cell and outside-out patch-clamp recordings from granule cells in acute cerebellar slices, we found that migrating granule cells begin to express AMPA receptors before they arrive in the internal granule cell layer and receive synaptic input. ![]() The single-channel properties of AMPA receptors can affect information processing in neurons by influencing the amplitude and kinetics of synaptic currents, yet little is known about the unitary properties of native AMPA receptors in situ.
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