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.
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Dipartimento di Medicina Sperimentale e Scienze Biochimiche II Università degli Studi di Roma Tor Vergata, Italy.
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D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000096:biosynthesis*; D018092:Kainic Acid Receptors / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007334:Insulin-Like Growth Factor I; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D011994:Recombinant Proteins