Premium
The effects of temperature on the interactions between volatile general anaesthetics and a neuronal nicotinic acetylcholine receptor
Author(s) -
Dickinson R.,
Lieb W.R.,
Franks N.P.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15949.x
Subject(s) - chemistry , acetylcholine receptor , acetylcholine , nicotinic agonist , receptor , dissociation constant , biophysics , halothane , nicotinic acetylcholine receptor , endocrinology , biochemistry , biology , organic chemistry
1 Completely isolated identified neurones from the right parietal ganglion of the pond snail Lymnaea stagnalis were investigated under two‐electrode voltage clamp. Neuronal nicotinic acetylcholine receptor (AChR) currents were studied at low acetylcholine concentrations (≤200 nM). 2 Inhibition of the ACh‐induced currents by three volatile general anaesthetics (halothane, isoflurane and methoxyflurane) and the specific inhibitor (+)‐tubocurarine was studied as a function of temperature (over the range 4–25°C). 3 The inhibition by the volatile anaesthetics increased (inhibition constants decreased) with decreasing temperature while the inhibition by (+)‐tubocurarine did not change significantly near room temperature, but decreased at lower temperatures. The (+)‐tubocurarine inhibition appeared to be competitive in nature and showed no significant voltage‐dependence. 4 The van't Hoff plots, (logarithms of the dissociation constants against reciprocal absolute temperature) were linear for the anaesthetics, but markedly non‐linear for (+)‐tubocurarine. From these plots, values for the changes in the standard Gibbs free energy ΔG° water→AChR , enthalpy ΔH° water→.AChR , entropy ΔS° water→AChR and heat capacity ΔC° p water→AChR were determined. Tubocurarine was found to bind very much tighter to the receptor than the volatile anaesthetics due, entirely, to a favourable increase in entropy on binding. 5 A comparison between the temperature‐dependence of the anaesthetic inhibition of the ACh receptor and that of general anaesthetic potencies in animals indicates that the temperature‐dependence of animal potencies might be simply accounted for in terms of changes in anaesthetic/receptor binding.