Inhibition of [3H]kainic acid receptor binding by divalent cations correlates with ion affinity for the calcium channel.

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.