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 ph enotype (EAA-) of rat cerebellar granule cells becomes EAA sensitive ( EAA+) when cultured in the presence of human recombinant IGF-I. In ord er 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 st udy macroscopic currents evoked by the application in the bath of kain ate to (EAA-) and (EAA+) neurons, and compared their properties to sis ter 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-cu ltured neurons. The amplitude of the responses induced by kainate was a linear function of the membrane potential in the three groups of cel ls and the reversal potential of the currents was about 0 mV, suggesti ng that the general property of each channel is identical in all three types of neurons while the different conductances observed are due ei ther to a decreased expression, a different permeability or an altered affinity of the single receptor.