Subunit Composition, Kinetic, and Permeation Properties of AMPA Receptors in Single Neocortical Nonpyramidal Cells

Abstract

Native AMPA receptors (AMPARs) were investigated in neocortical fast-spiking (FS) and regular-spiking nonpyramidal (RSNP) cells. The onset of and recovery from desensitization as well as current rectification and single-channel conductance were studied by using fast glutamate application to outside-out patches. The GluR1-4 subunit, flip/flop splicing, and R/G editing expression patterns of functionally characterized cells were determined by single-cell reverse transcription-PCR to correlate the subunit composition of native AMPARs with their functional properties. Our sample, mostly constituted by RSNP neurons, predominantly expressed GluR3 flip and GluR2 flop. In individual cells, flip/flop splicing of each subunit appeared to be regulated independently, whereas for R/G editing all subunits were either almost fully edited or unedited. We confirmed that the relative GluR2 expression controls the permeation properties of native AMPARs, whereas none of the single molecular parameters considered appeared to be a key determinant of the kinetics. FS neurons displayed AMPARs with relatively homogeneous functional properties characterized by fast desensitization, slow recovery from desensitization, marked inward rectification, and large single-channel conductance. In contrast, these parameters varied over a wide range in RSNP neurons, and their combination resulted in various AMPAR functional patterns. Indeed, in different cells, fast or slow desensitization was found to be associated with either slow or fast recovery from desensitization. Similarly, fast or slow kinetics was associated with either strong or weak rectification. Our results suggest that kinetic and permeation properties of native AMPARs can be regulated independently in cortical neurons and probably do not have the same molecular determinants. AMPA receptor; neocortex; interneuron; single-cell RT-PCR; fast glutamate application; subunit; splicing; editingThe fast excitatory synaptic transmission in the C NS is mediated mainly by AM PA receptor channels (AM PARs). These receptors are multimeric assemblies of four different subunits GluR1-4 (for review, see Wisden and Seeburg, 1993;Hollmann and Heinemann, 1994). Further diversity is generated by alternative splicing (Sommer et al., 1990) and mRNA editing (Sommer et al., 1991;L omeli et al., 1994). In heterologous expression systems recombinant AM PAR permeation properties are controlled by the relative abundance of GluR2 (for review on voltage dependence and calcium permeability, see Hollmann and Heinemann, 1994;Jonas and Burnashev, 1995) [see also Swanson et al. (1997) for single channel conductance]. In contrast, their kinetic properties are affected by multiple factors, including subunit composition, flip/flop alternative splicing, and mRNA edition at the R/G site (Sommer et al., 1990;L omeli et al., 1994;Mosbacher et al., 1994;Partin et al., 1994).Studies of native AM PARs by patch-clamp recordings combined with single-cell reverse transcription-PCR (single-cell RT-PCR; Lambolez et al., 1992) have con...

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

“…AMPA receptor-mediated currents rise and decay faster in interneurons than in principal neurons, in part because of different subunit profiles (30)(31)(32). Electrophysiological studies indicate that, in hippocampus, pyramidal͞interneuron synaptic connections are powerful and elicit action potentials at short latency, even in resting conditions, when only one or a few presynaptic cells fire (19,24).…”

A neurochemical signature of visual recovery after extrastriate cortical damage in the adult cat

“…Previous reports in rodents (Geiger et al, 1995;Vissavajjhala et al, 1996;Angulo et al, 1997;Kondo et al, 1997) and primates (Vickers et al, 1993;Munoz et al, 1999) suggest that some classes of cortical neurons, including those expressing calcium-binding proteins, can be differentiated by their expression of different AMPA receptor subunits. However, our present experiments revealed that in normal cats, the great majority of calbindin-and parvalbuminpositive cells, and the majority of LS-projecting pyramidal cells in layer II/III of area 18 expressed all four subunits of the AMPA receptor.…”

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Selective Excitation of Subtypes of Neocortical Interneurons by Nicotinic Receptors

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