Ca2+ permeability and joro spider toxin sensitivity of AMPA and kainate receptors on cerebellar granule cells.

We have investigated the Ca2+ permeability of native kainate- and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate- (AMPA) receptors in cultured rat cerebellar granule cells. Intracellular Ca2+ ([Ca2+]i) increases and Mn2+ quench of fura-2 (a measure of Ca2+ entry) mediated by kainate receptors were completely dependent on the presence of extracellular Na+. Kainate receptor-mediated [Ca2+]i rises were reduced 37% by the L-type voltage-gated Ca2+ channel blocker nifedipine (1 microM). AMPA receptor-mediated [Ca2+]i rises observed in Na+-free buffer were sensitive to Joro spider toxin (500 nM) blockade showing a 65% reduction, while kainate receptor-mediated [Ca2+]i responses were largely insensitive. These results suggest that a component of AMPA receptor-mediated [Ca2+]i increases occurs through Ca2+ permeable receptors which lack the GluR2 subunit and are Joro spider toxin sensitive. In contrast, kainate receptors do not appear to directly gate significant Ca2+ but raise [Ca2+]i through activation of voltage-gated Ca2+ channels and seem largely insensitive to Joro spider toxin.