CALCIUM REGULATION OF AGONIST BINDING TO ALPHA-7-TYPE NICOTINIC ACETYLCHOLINE-RECEPTORS IN ADULT AND FETAL-RAT HIPPOCAMPUS

Quantitative autoradiography was used to compare the binding propertie s of alpha 7-type nicotinic acetylcholine receptors in fetal and adult rat hippocampus. Whereas there were high levels of I-125-alpha-bungar otoxin (I-125-alpha-BTX) binding throughout fetal hippocampal field CA 1, there was a significant decrease in binding site density in the adu lt. The affinity of I-125-alpha-BTX binding, as well as alpha-cobratox in and nicotine potency to displace I-125-alpha- BTX, did not change w ith age. Addition of Ca2+ to the assay buffer did not alter I-125-alph a-BTX binding, or alpha-co-bratoxin inhibition of I-125-alpha-BTX bind ing, although it significantly increased nicotine affinity at both age s. 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 coope rativity of nicotine displacement curves in stratum oriens of the adul t, but not in the fetus. These findings indicate that the properties o f 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 pot entiation of agonist binding to a desensitized state of the alpha 7 ni cotinic acetylcholine receptor and may represent an important neuropro tective mechanism.