title: Inhibition of [3H]kainic acid receptor binding by divalent cations correlates with ion affinity for the calcium channel.
abstract: Since the neurotoxicity of kainic acid may be due to the opening of membrane channels for calcium ions for (Ca2+), the effects of Ca2+ and other cations were examined on the specific binding of [3H]kainic acid to membranes from the forebrain of the rat. [3H]Kainic acid bound to a high affinity site (KD = 5.6 nM) that was inhibited in a concentration-dependent manner by Ca2+ ions with an IC50 of 3.2 mM. In the presence of 1 mM Ca2+, the KD of the binding of [3K]kainic acid increased to 11.1 nM without any change in the Bmax. The divalent cations, manganese and cobalt, also were potent inhibitors of the binding of [3H]kainic acid, while barium and strontium were much weaker. The inhibitory effects of Ca2+ on the binding of [3H]kainic acid were blocked by the inorganic Ca2+ channel blockers, cadmium and lanthanum. These data suggest that Ca2+ modulates the binding affinity [3H]kainic acid through an allosteric interaction between the binding site on the Ca2+ channel and the kainic acid receptor.
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology*; D007473:Ion Channels / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium
chemical_list: D002118:Calcium; D002413:Cations, Divalent; D007473:Ion Channels; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter; D014316:Tritium