Cortical neurones with Ca2+permeable AMPA/kainate channels display distinct receptor immunoreactivity and are GABAergic

Abstract

A minority subset of cortical neurones exhibit kainate-activated Co2+uptake, a marker for AMPA/kainate receptor gated Ca2+-permeable channels. Consistent with enhanced Ca2+influx through these channels, Co2+-positive neurones are unusually vulnerable to death induced by exposure to either AMPA or kainate. Here we show that Co2+-positive cortical neurones express a distinctive profile of AMPA receptor subunits as determined by immunostaining. Co2+-positive neurones were much less likely to express GluR2/GluR3, and much more likely to express GluR1 or GluR4, than the general cortical neuronal population. Thus expression of AMPA receptors lacking the GluR2 subunit may explain the Co2+staining, and selective vulnerability to kainate exhibited by Co2+-positive cells. Almost all GABAergic neurones, identified by immunostaining for glutamic acid decarboxylase, were Co2+-positive. The widespread presence of Ca2+-permeable AMPA/kainate receptor-gated channels on cortical GABAergic neurones may have important implications for the fate of cortical inhibition in disease states associated with the excitotoxic overstimulation of glutamate receptors.

Keywords

• AMPA
• calcium
• cell culture
• glutamate
• GABA
• kainate