Calcium regulation of agonist binding to α7-type nicotinic acetylcholine receptors in adult and fetal rat hippocampus

Quantitative autoradiography was used to compare the binding properties of alpha 7-type nicotinic acetylcholine receptors in fetal and adult rat hippocampus. Whereas there were high levels of I-125-alpha-bungarotoxin (I-125-alpha-BTX) binding throughout fetal hippocampal field CA1, there was a significant decrease in binding site density in the adult. The affinity of I-125-alpha-BTX binding, as well as alpha-cobratoxin and nicotine potency to displace I-125-alpha- BTX, did not change with age. Addition of Ca2+ to the assay buffer did not alter I-125-alpha-BTX binding, or alpha-co-bratoxin inhibition of I-125-alpha-BTX binding, although it significantly increased nicotine affinity at both ages. The effect of Ca2+ on agonist affinity was dose-dependent, with an EC50 value of 0.25-0.5 mM. Ca2+ also significantly increased the cooperativity of nicotine displacement curves in stratum oriens of the adult, but not in the fetus. These findings indicate that the properties of hippocampal I-125-alpha-BTX binding sites are largely similar across age. Ca2+ selectively enhances the affinity of agonist binding, with no change in antagonist binding. This ionic effect may result from potentiation of agonist binding to a desensitized state of the alpha 7 nicotinic acetylcholine receptor and may represent an important neuroprotective mechanism.