Selective block of AMPA/kainate receptors of hippocampal interneurons as a new approach to the investigation of inhibitory system.

Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, Thorez pr. 44, St. Petersburg, 194223, Russia.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 09/1998; 83(5-6):19-39. DOI: 10.1007/BF02463025
Source: PubMed


Effects of open channel blockers of AMPA/kainate receptors have been examined using whole cell recordings and kainate application in the neurons freshly isolated by vibrodissociation from the rat hippocampal slice preparation. Although the hippocampal neurons differed little in the voltage-current relations and sensitivity to kainate, a prominent difference was found in their susceptibility to the blocking action of adamantane derivatives studied. The pyramidal neurons had low sensitivity to the open channel blockers but the neurons which might be assigned most probably to the group of inhibitory interneurons proved to be highly sensitive. A group of neurons of intermediate sensitivity have also been found. The ability of the same blocking drugs to depress the excitatory inputs in the inhibitory interneurons has been demonstrated in the experiments on the hippocampal slice preparation. Enhancement of the field spike and excitatory postsynaptic potential amplitude was observed in the presence of adamantane derivatives. An additional treatment of the preparation with a GABA receptor antagonist, bicuculline, did not potentiate this effect. In conclusion, the observed difference in the pharmacological properties of inhibitory interneurons may be effectively used for detailed analysis of the brain synaptic transmission.

2 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: The properties of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors were examined in various cell types isolated from young rat hippocampus, striatum and cerebellum using patch-clamp and fast application techniques. A dicationic adamantane derivative, IEM-1460, reversibly inhibited kainate-induced currents. In the presence of 100 microM IEM-1460, kainate currents in striatal giant cholinergic interneurons and hippocampal non-pyramidal neurons were inhibited by 95% and 81%, respectively, at Vh = - 70 mV. Striatal GABAergic principal cells, hippocampal pyramidal neurons and cerebellar Purkinje cells had low sensitivity to IEM-1460 (inhibition by 4-15%). Analysis of averaged data from the cell types studied revealed a highly significant positive correlation (r= 0.93, P < 0.01) between percentage inhibition by 100 microM IEM-1460 and relative calcium permeability of AMPA receptors, P(Ca)/P(Na). Also, within each brain structure, the sensitivity of IEM-1460 block was lower the stronger the outward rectification of kainate currents. Some hippocampal neurons exhibited intermediate sensitivity to IEM-1460. Kainate currents were suppressed by 40% in the presence of 100 microM IEM-1460. Meanwhile, AMPA receptors in this cell type had low calcium permeability (P(Ca)/P(Na) = 0.13) and demonstrated outwardly rectifying kainate currents. The interrelation of different properties of AMPA receptors considering their assembly is discussed. The data obtained suggest that IEM-1460 may be a convenient and promising marker of native AMPA receptor assembly: it selectively inhibits Ca(2+)-permeable, GluR2-lacking AMPA receptors.
    Neuroscience 09/1999; 94(1):261-8. DOI:10.1016/S0306-4522(99)00326-7 · 3.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This article reviews current progress in studies of the relationship between the molecular structure of different subtypes of AMPA receptors and their functional properties. Differences in the subunit composition of AMPA receptors involved in glutamatergic synaptic inputs to efferent (main) neurons and interneurons are discussed with reference to neurons isolated from the hippocampus, striatum, and cerebellum. Data on the possibility of selective pharmacological actions on the ion channels of different AMPA receptor subtypes are presented; this allows these receptors to be identified and their functions to be studied in greater depth in normal and pathological conditions.
    Neuroscience and Behavioral Physiology 01/2000; 30(1):27-35. DOI:10.1007/BF02461389
  • [Show abstract] [Hide abstract]
    ABSTRACT: Experiments were performed on isolated neurons from hippocampal field CA1 and the dentate fascia to identify the subunit composition and distribution of splicing variants of AMPA receptor subunits. Currents evoked by the application of kainate were recorded using a whole-cell patch clamping method. The presence of GluR2 subunits in receptors was associated with a sharp reduction in the activity of the selective channel blocker IEM-1460. The composition of flip versions of subunits was assessed using cyclothiazide. AMPA receptors in the major cell types (pyramidal and granule cells) had low sensitivity to IEM-1460, while AMPA receptors of other cells (interneurons) had high or intermediate sensitivity. Cyclothiazide had strong potentiating effects on the main cell types in both structures as compared with interneurons. Thus, there is a correlation between the sensitivities of hippocampal neurons to IEM-1460 and cyclothiazide. The main cell types in both structures expressed large quantities of the GluR2 subunit in their AMPA receptors, with high levels of flip subunits, as compared with the other cell types, in which GluR2 subunits were virtually absent and the flop version predominated. This appears to reflect the functional features of different types of neurons.
    Neuroscience and Behavioral Physiology 02/2001; 31(2):219-25. DOI:10.1023/A:1005276627192
Show more