Heterogeneous conductance levels of native AMPA receptors

The single-channel properties of AMPA receptors can affect information proc essing in neurons by influencing the amplitude and kinetics of synaptic cur rents, yet little is known about the unitary properties of native AMPA rece ptors in situ. 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 gr anule cell layer and receive synaptic input. At saturating agonist concentr ations, the open probability of channels in outside-out patches from migrat ing cells was very high, allowing us to identify patches that contained onl y one or two active channels. Analysis of the single-channel activity in th ese patches showed that individual AMPA receptors exhibit as many as four d istinguishable conductance levels. The conductance levels observed varied s ubstantially for different channels, although on average the values fell wi thin the range of unitary conductances estimated previously for synaptic AM PA receptors. In contrast to patches from migrating granule cells, we rarel y observed directly resolvable single-channel currents in patches excised f rom the somata of granule cells in the internal granular layer, even though these cells gave large AMPA receptor whole-cell currents. We did, however, detect AMPA receptors with apparent unitary conductances of <1 pS in patch es from both migrating and mature granule cells. Our results suggest that g ranule cells express a heterogeneous population of AMPA receptors, a subset of which are segregated to postsynaptic sites after synaptogenesis.