AMPA KAINATE RECEPTOR ACTIVATION INHIBITS NEURONAL DELAYED RECTIFIER K+ CURRENT VIA NA+ ENTRY IN RAT CORTICAL-NEURONS/

In the present study we evaluated the modulation of neuronal delayed r ectifier K+ current (I-K) by activation of ionotropic glutamate recept ors. In whole-cell voltage-clamp experiments, an external application of 10-100 mu M kainate suppressed the amplitude of I-K following an in ward shift of holding current. The effect of kainate on I-K was elimin ated by CN QX, an AMPA/kainate receptor antagonist, indicating that th e receptor-mediated cation entry caused I-K suppression, When external Na+ was completely replaced by equimolar choline(+) or N-methyl-D-glu camine, kainate-induced I-K suppression was abolished, Our results sug gest that in cultured rat cortical neurons, AMPA/kainate receptor acti vation leads to an intracellular Na+ increase which blocks delayed rec tifier K+ channels, This contributes to feed-forward excitation of neu ronal cells in glutaminergic responses. (C) 1998 Academic Press.