Binding studies of Mn+2 to isolated acetylcholine receptor as a probe for cation-receptor interaction. |
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Authors: | M Mihovilovic T Nowak M A Raftery M Martinez-Carrion |
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Institution: | Department of Chemistry, University of Notre Dame, Notre Dame, IN 46556 USA |
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Abstract: | The paramagnetic cation Mn+2 binds to acetylcholine receptor (AcChR) at sites with at least two different affinity constants. For each α-Bungarotoxin (α-Bgt) binding site AcChR has between 3 to 4 Mn+2 sites with Kd values of 1.74 ± 1.0 × 10?4 M. An additional 10–12 sites/α-Bgt site have a weaker affinity for Mn+2 (Kd ? 1 mM). The α-Bgt does not displace bound Mn+2, however Ca+2 displaces all bound Mn+2 in a competitive fashion with Kd of 0.90 × 10?3 M and Mg+2 is as effective as Ca+2 in the displacement. Decamethonium, carbamylcholine and NaCl at high concentrations are also effective in displacing Mn+2. A constant enhancement value (?b) for the binary metal · AcChR complexes was obtained when simultaneous EPR measurements and the water proton relaxation rates were made. Similarity of the AcChR environment and/or coordination number for the Mn+2 sites in AcChR is inferred. It appears that Mn+2 binds to many AcChR sites, different from those responsible for binding cholinergic ligands. The Mn+2 site seem to be the same as those responsible for binding the electrophysiologically significant Ca+2. |
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Keywords: | NIH Career Development Awardee To whom to address correspondence |
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