Effects of several inhalation anaesthetics on the kinetics of postsynaptic conductance changes in mouse diaphragm

1 Miniature endplate currents were recorded with extracellular electrodes in mouse diaphragms in order to measure the kinetics of the conductance change produced by acetylcholine. Miniature endplate potentials (m.e.p.ps) were recorded intracellularly in the same fibres in which the currents were being recoreded. 2 The general anaesthetics, ether, halothane, chloroform and enflurane at low (anaesthetic) concentrations increased the rate of decay of miniature endplate currents (m.e.p.cs) and reduced the amplitude of m.e.p.ps in this way. 3 At high concentrations the anaesthetics caused a reduction in the amplitude of both m.e.p.cs and m.e.p.ps, and a decrease in the rate of decay of the currents. With halothane and enflurane the decay of some currents became biphasic, with a prolonged tail. 4 It was proposed that the increased rate of decay of the conductance caused by the four agents at anaesthetic concentrations is due to an increase in the fluidity of the subsynaptic membrane. Prolongation of the currents at higher concentrations may be caused by an increase in membrane dielectric constant. 5 The effectiveness of the four anaesthetics in producing a 30% decrease in the time constant of decay of m.e.p.cs was shown to be related to their oil/water partition coefficients and followed closely the relationship between anaesthetic potency and oil/water partition coefficient. It is suggested therefore that the four anaesthetics may produce anaesthesia by changing the kinetics of postsynaptic conductance changes at synapses, perphaps by increasing membrane fluidity.