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Research ArticleArticle

Ion Exchange between Agonists and Inorganic Ions at the Acetylcholine Receptor of Torpedo californica

CHARLES E. SPIVAK and DERMOT B. TAYLOR
Molecular Pharmacology November 1980, 18 (3) 413-420;
CHARLES E. SPIVAK
Department of Pharmacology and Brain Research Institute, U.C.L.A., School of Medicine, Los Angeles, California 90024
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DERMOT B. TAYLOR
Department of Pharmacology and Brain Research Institute, U.C.L.A., School of Medicine, Los Angeles, California 90024
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Abstract

Our objective was to investigate the nature of the reactions by which agonists trigger the nicotinic acetylcholine receptor. A series of experiments on the binding of tritiated decamethonium and muscarone to the particulate-bound nicotinic acetylcholine receptor from Torpedo californica was carried out using a filtration assay. Specific binding was assessed by subtracting the nonspecific binding, found when the receptors were saturated with α-bungarotoxin, from the total binding. The binding curves obtained by varying the concentration of the physiological ions can be explained by stoichiometric ion-exchange equations, in accordance with the principle of electroneutrality, without invoking positive and negative cooperativity or complicated ad hoc assumptions. In all of our experiments, saturation of the receptors was produced by equimolar quantities of decamethonium, muscarone, and α-bungarotoxin. These results indicated that an additional anchoring or acceptor site is required to bind decamethonium and that decamethonium is monovalent at the receptor site. The receptor recognition site can change its electrovalence and exchange divalent or monovalent counter ions for either decamethonium or muscarone, depending on the agonist and the ionic environment. In all our experiments the receptor behaved with an electrovalence of either one or two and never with an intermediate value. Using decamethonium and low calcium concentrations (5 mM) the receptor exchanged one decamethonium for one magnesium ion, whereas at higher calcium concentrations (15 mM and above) it exchanged one decamethonium for two monovalent cations. Calcium ions do this by acting on sites other than the agonist recognition site. Similar effects of calcium ions were seen with muscarone. In the divalent state the receptor’s recognition site binds Mg2+ but not Ca2+, and in the monovalent state it binds K+ but not Na+. Attempts to analyze the data in terms of other ionic models were unsuccessful.

  • Copyright © 1980 by The American Society for Pharmacology and Experimental Therapeutics

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Molecular Pharmacology
Vol. 18, Issue 3
1 Nov 1980
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Research ArticleArticle

Ion Exchange between Agonists and Inorganic Ions at the Acetylcholine Receptor of Torpedo californica

CHARLES E. SPIVAK and DERMOT B. TAYLOR
Molecular Pharmacology November 1, 1980, 18 (3) 413-420;

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Research ArticleArticle

Ion Exchange between Agonists and Inorganic Ions at the Acetylcholine Receptor of Torpedo californica

CHARLES E. SPIVAK and DERMOT B. TAYLOR
Molecular Pharmacology November 1, 1980, 18 (3) 413-420;
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