Pharmacologic analysis of the subunit composition of AMPA-receptors in the hippocampal neurons

Subunit composition and abundance of flip version of different AMPA receptor subunits were studied in neurons acutely isolated from hippocampal area CA1 and dentate gyrus. Whole cell recordings were made to record kainate unduced currents. Presence of GluR2 in the receptor complex led to significant decrease of selective channel blocker IEM-1460 potency. Flip versions of AMPA receptor subunits were discriminated on the basis of their sensitivity to cyclothiazide. Principal cell AMPA receptors in both areas were characterized by low sensitivity to IEM-1460 while AMPA receptors of nonprinciple cells exhibited high or intermediate sensitivity to IEM-1460. We observed significantly larger potentiating effect of cyclothiazide on principal cells. Our data indicate that there is a correlation between low sensitivity to IEM-1460 and high sensitivity to cyclothiazide among AMPA receptors of different cells. Principal cells in both regions possess more GluR2 subunits in their AMPA receptor complexes and more abundant flip versions of their subunits in comparison with nonprincipal cells. This correlation is obviously related to functional pecularities of different neurons.