Conformational states of the nicotinic acetylcholine receptor from Torpedo californica induced by the binding of agonists, antagonists, and local anesthetics. Equilibrium measurements using tritium-hydrogen exchange

Journal Article · Tue Jan 10 04:00:00 EST 1989 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00427a007· OSTI ID:6030662

McCarthy, M P; Stroud, R M

The tritium-hydrogen exchange kinetics of Torpedo californica AChR, in native membrane vesicles at pH 7.4 and 0 degrees C, have been analyzed in the presence of agonists, partial agonists, local anesthetics, and competitive antagonists. The agonists carbamylcholine (10 microM-1 mM) and suberyldicholine (10 microM) and the partial agonists decamethonium (25 microM and 1 mM) and hexamethonium (1 mM) have no effect on the exchange kinetics, although at lower concentration carbamylcholine may slightly accelerate exchange. Nondesensitizing local anesthetics do affect the exchange behavior, dependent on concentration. Procaine at 500 microM moderately retards exchange while procaine at 10 mM and tetracaine at 5 mM slightly accelerate exchange. The competitive antagonist alpha-bungarotoxin retards exchange significantly, as does d-tubocurarine although to a lesser extent. These results suggest that the resting and desensitized conformations of the AChR are very similar in overall solvent accessibility and that at lower concentrations noncompetitive blockers such as procaine may stabilize a less solvent-accessible state of the AChR. The competitive antagonists alpha-bungarotoxin and d-tubocurare also stabilize a dynamically restricted, less solvent-accessible conformation of the acetylcholine receptor, demonstrating that a large conformational change accompanies binding of these toxins. Any change in conformation which may accompany desensitization is very different from these effects.

• Research Organization: Univ. of California, San Francisco (USA)
• OSTI ID: 6030662
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 28:1; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
AMINES
AMMONIUM COMPOUNDS
ANESTHETICS
ANIMALS
ANTIGENS
AQUATIC ORGANISMS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ELEMENTS
ESTERS
FISHES
HYDROGEN
IN VITRO
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
NEUROREGULATORS
NONMETALS
ORGANIC COMPOUNDS
PARASYMPATHOMIMETICS
PROCAINE
PROTEINS
QUATERNARY COMPOUNDS
REACTION KINETICS
RECEPTORS
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES