Calcium Regulation of Agonist Binding to α7-Type Nicotinic Acetylcholine Receptors in Adult and Fetal Rat Hippocampus

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Abstract

Abstract:

Quantitative autoradiography was used to compare the binding properties of α7-type nicotinic acetylcholine receptors in fetal and adult rat hippocampus. Whereas there were high levels of 125I-α-bungarotoxin (125I-α-BTX) binding throughout fetal hippocampal field CA1, there was a significant decrease in binding site density in the adult. The affinity of 125I-α-BTX binding, as well as α-cobratoxin and nicotine potency to displace 125I-α-BTX, did not change with age. Addition of Ca2+ to the assay buffer did not alter 125 I-α-BTX binding, or α-cobratoxin inhibition of 125I-α-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 125I-α-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 α7 nicotinic acetylcholine receptor and may represent an important neuroprotective mechanism.

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