Human recombinant IGF-I induces the functional expression of AMPA/kainate receptors in cerebellar granule cells

We have previously reported that an excitatory amino acid resistant phenotype (EAA-) of rat cerebellar granule cells becomes EAA sensitive (EAA+) when cultured in the presence of human recombinant IGF-I. In order to assess the mechanism through which this somatomedin upmodulates the functional expression of EAAs receptors, we have performed studies using the whole-cell configuration of the patch-clamp technique to study macroscopic currents evoked by the application in the bath of kainate to (EAA-) and (EAA+) neurons, and compared their properties to sister cultures grown in classical conditions employing whole foetal calf serum (FCS). Kainate elicited macroscopic, 6-cyano-7-nitroquinoxaline-2,3-dione sensitive, inward currents at a holding potential of -60 mV in almost all the patched cells but the mean amplitude of the current was consistently smaller in (EAA-) neurons compared to (EAA+) neurons although the amplitude was still smaller than that observed in FCS-cultured neurons. The amplitude of the responses induced by kainate was a linear function of the membrane potential in the three groups of cells and the reversal potential of the currents was about 0 mV, suggesting that the general property of each channel is identical in all three types of neurons while the different conductances observed are due either to a decreased expression, a different permeability or an altered affinity of the single receptor.