Glial Cells in the Mouse Hippocampus Express AMPA Receptors with an Intermediate Ca2+ Permeability

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Abstract
Recently, we could demonstrate the 'complex' glial cells in mouse hippocampal slices express glutamate receptor changes of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate subtypes. In the present study, we further characterized this glial receptor. Since voltage-clamp control is imperfect and diffusion barriers hinders the quantitative analysis of the receptor currents in situ, the patch-clamp technique was applied to glial cells acutely isolated from the mouse hippocampal CA1 stratum radiatum subregion. A concentration-clamp technique was used which enabled very fast exchange of the extracellular solutions. Thus, it was possible to characterize the transient receptor currents with high time resolution. Application of L-glutamate, AMPA and L-homocysteate induced rapidly activating and fast desensitizing receptor currents in the suspended glial cells. In contrast, kainate induced non-desensitizing currents. The corresponding dose-response curve revealed a half-maximum of current activation at 350 microM. The current/voltage relationship of the kainate-evoked response was linear with a reversal potential at approximately 9 mV. Analysis of the reversal potential in solutions containing high concentrations of CaCl2 confirmed earlier in situ data by demonstrating significant Ca2+ permeability of the glial glutamate receptor channels in the hippocampus. The kainate-induced receptor currents were markedly increased by cyclothiazide, a substance which selectively potentiates glutamate receptors of the AMPA subtype. We conclude that glial cells of the juvenile hippocampus mainly express heteromeric high-affinity AMPA receptors. Most probably, the receptor channels are assembled from the low Ca(2+)-permeable glutamate receptor-2 subunit together with Ca(2+)-permeable AMPA-preferring subunits.