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.
Division of Neuroscience, School of Biological Sciences, University of Manchester, UK. monsejs2@fs2.scg.man.ac.uk
J R
JR
Savidge
D R
DR
Bristow
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016257:Fura-2; D008345:Manganese; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology*
D001569:Benzodiazepines; D002118:Calcium; D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D016257:Fura-2; D008345:Manganese; D009543:Nifedipine; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D012964:Sodium; D013111:Spider Venoms; C044936:JSTX spider toxin; C079692:GYKI 53655