title: Temperature dependence of acetylcholine receptor channels activated by different agonists.
abstract: The temperature dependence of agonist binding and channel gating were measured for wild-type adult neuromuscular acetylcholine receptors activated by acetylcholine, carbamylcholine, or choline. With acetylcholine, temperature changed the gating rate constants (Q(10) ≈ 3.2) but had almost no effect on the equilibrium constant. The enthalpy change associated with gating was agonist-dependent, but for all three ligands it was approximately equal to the corresponding free-energy change. The equilibrium dissociation constant of the resting conformation (K(d)), the slope of the rate-equilibrium free-energy relationship (Φ), and the acetylcholine association and dissociation rate constants were approximately temperature-independent. In the mutant αG153S, the choline association and dissociation rate constants were temperature-dependent (Q(10) ≈ 7.4) but K(d) was not. By combining two independent mutations, we were able to compensate for the catalytic effect of temperature on the decay time constant of a synaptic current. At mouse body temperature, the channel-opening and -closing rate constants are ∼400 and 16 ms(-1). We hypothesize that the agonist dependence of the gating enthalpy change is associated with differences in ligand binding, specifically to the open-channel conformation of the protein.
authors.affiliation: Department of Physiology and Biophysics, State University of New York, Buffalo, New York, USA.
authors.forename: Shaweta
authors.initials: S
authors.lastname: Gupta
authors.forename: Anthony
authors.initials: A
authors.lastname: Auerbach
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013696:Temperature
chemical_list: D018679:Cholinergic Agonists; D011950:Receptors, Cholinergic; D002217:Carbachol; D000109:Acetylcholine