CA2-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONATE (AMPA) RECEPTORS IN ISOLATED INTERNEURONS FROM THE OLFACTORY-BULB OF THE RAT( ION PERMEABILITY PROPERTIES OF (R,S)ALPHA)

The aim of the study was to investigate the divalent cation permeabili ty of native a-amino-3-hydroxy-5-methyl-4-isoxazole-priopionate (AMPA) receptors expressed in interneurons of the olfactory bulb. Kainic aci d(KA) was used as agonist to activate AMPA-receptor-mediated currents. which were recorded with the use of the patch-clamp technique. In int erneurons acutely isolated from the olfactory bulb, the current respon ses to KA showed linear/outwardly rectifying current-voltage (I-V) rel ationships with a positive average reversal potential of +7 mV in norm al external medium (1 mM Ca2+, 1 mM Mg2+). Raising the external Ca2+ c oncentration to 10 mM suppressed the amplitude, whereas omission of Ca 2+ enhanced the amplitude of the current. Spectral analysis of the inc rease in current variance produced by KA indicated that the decreased amplitude observed in 10 mM Ca2+ was accompanied by a reduction in the apparent single-channel conductance. Raising the concentration of Mg2 + from 1 to 10 mM had a weak depressant effect on the KA-evoked curren t amplitude. No shift in the reversal potential was observed when the concentration of Ca2+ or Mg2+ was changed from 1 to 10 mM. Increasing the external medium concentration of Ca2+ to 60 mM not only further de pressed the amplitudes of the KA-evoked currents but also gave a prono unced leftward shift in the average reversal potential to -32 +/- 9 (S E) mV (N = 7). For neurons in primary culture, current responses to KA also showed linear/outwardly rectifying I-V relationships with a posi tive average reversal potential in normal external medium. Substitutin g N-methylglucamine for Na+ and increasing the Ca2+ concentration to 1 0 mM gave a leftward shift in the average reversal potential from +9 /- 3 mV to -47 +/- 4 mV (N = 11) and caused a marked reduction in the amplitude of the KA-evoked currents at negative potentials. The permea bility properties of the studied AMPA receptors were well predicted by the Eyring rate model (symmetrical, 2 barriers, 1 site). The model ga ve a pCa(2+)/pK(+) permeability ratio of 0.06 for acutely isolated int erneurons and 0.14 for interneurons in primary culture. The constant f ield theory, which failed to successfully reproduce all the experiment al data, gave corresponding low permeability ratios of 0.18 and 0.40 f or acutely isolated cells and cells in primary culture, respectively. Thus it is concluded that interneurons in the olfactory bulb mainly ex press AMPA receptors with low permeability to Ca2+ ions.