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 (?), and the acetylcholine association and dissociation rate constants were approximately temperature-independent. In the mutant ?G153S, 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.

SUBMITTER: Gupta S 

PROVIDER: S-EPMC3037575 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature