Calcium regulation of agonist binding to alpha7-type nicotinic acetylcholine receptors in adult and fetal rat hippocampus.
Quantitative autoradiography was used to compare the binding properties of alpha7-type nicotinic acetylcholine receptors in fetal and adult rat hippocampus. Whereas there were high levels of 125I-alpha-bungarotoxin (125I-alpha-BTX) binding throughout fetal hippocampal field CA1, there was a significant decrease in binding site density in the adult. The affinity of 125I-alpha-BTX binding, as well as alpha-cobratoxin and nicotine potency to displace 125I-alpha-BTX, did not change with age. Addition of Ca2+ to the assay buffer did not alter 125I-alpha-BTX binding, or alpha-cobratoxin inhibition of 125I-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 125I-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 alpha7 nicotinic acetylcholine receptor and may represent an important neuroprotective mechanism.
Ospina
J A
JA
Department of Pharmacology, College of Medicine, University of California, Irvine 92697, USA.
Broide
R S
RS
Acevedo
D
D
Robertson
R T
RT
Leslie
F M
FM
D000367:Age Factors; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D005333:Fetus / Q000737:chemistry / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry* / Q000378:metabolism; D007457:Iodine Radioisotopes; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*
D002038:Bungarotoxins; D007457:Iodine Radioisotopes; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D002118:Calcium