CONANTOKIN-G ANTAGONISM OF THE NMDA RECEPTOR SUBTYPE EXPRESSED IN CULTURED CEREBELLAR GRANULE CELLS

Conantokins are peptide antagonists of the N-methyl-D-aspartate (NMDA) subclass of excitatory amino acid receptors. We compared conantokin-G and AP5 antagonism of NMDA receptor activity expressed in cultures of neonatal rat cerebellar granule cells, using the fluorescent calcium indicator dye fura-2. The results were consistent with the binding of two molecules of agonist (NMDA) for channel activation and one antagonist molecule (AP5) for inhibition. However, conantokin-G antagonism was more complex: the peptide inhibited only similar to 70% of the elevation of intracellular free calcium produced by NMDA. These results, when combined with previous ones [8], suggest that conantokin-G may have different affinities for, and functional effects on, different subtypes of NMDA receptor complexes expressed in the mammalian CNS.