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Calcium Regulation of Agonist Binding to α7‐Type Nicotinic Acetylcholine Receptors in Adult and Fetal Rat Hippocampus
Author(s) -
Ospina Jose A.,
Broide Ron S.,
Acevedo Diana,
Robertson Richard T.,
Leslie Frances M.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70031061.x
Subject(s) - agonist , nicotinic agonist , endocrinology , medicine , chemistry , acetylcholine receptor , acetylcholine , binding site , nicotine , receptor , alpha 4 beta 2 nicotinic receptor , cooperative binding , nicotinic acetylcholine receptor , biology , biochemistry
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 125 I‐α‐bungarotoxin ( 125 I‐α‐BTX) binding throughout fetal hippocampal field CA1, there was a significant decrease in binding site density in the adult. The affinity of 125 I‐α‐BTX binding, as well as α‐cobratoxin and nicotine potency to displace 125 I‐α‐BTX, did not change with age. Addition of Ca 2+ to the assay buffer did not alter 125 I‐α‐BTX binding, or α‐cobratoxin inhibition of 125 I‐α‐BTX binding, although it significantly increased nicotine affinity at both ages. The effect of Ca 2+ on agonist affinity was dose‐dependent, with an EC 50 value of 0.25–0.5 m M . Ca 2+ 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 125 I‐α‐BTX binding sites are largely similar across age. Ca 2+ 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.