Halothane-induced changes in acetylcholine receptor channel kinetics are attenuated by cholesterol.
The single-channel recording technique was used to investigate the role of membrane lipids in the action of general anesthetics on ion channels. We examined the effects of halothane on acetylcholine receptor channels in Xenopus laevis myocytes in which the plasma membrane cholesterol level had been changed by pretreatment with cholesterol-rich or cholesterol-free liposomes. We found that the alteration in acetylcholine receptor channel kinetics, elicited in the presence of clinically-relevant concentrations of halothane, is attenuated when membrane cholesterol is increased and enhanced when membrane cholesterol concentration is decreased. These findings support the idea that general anesthetics interact with synaptic receptor channels indirectly through the lipid domains in which these synaptic proteins are embedded.
Lechleiter
J
J
Wells
M
M
Gruener
R
R
D000818:Animals; D002784:Cholesterol / Q000032:analysis / Q000502:physiology*; D006221:Halothane / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008081:Liposomes / Q000494:pharmacology; D008563:Membrane Lipids / Q000032:analysis / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D012995:Solubility; D014982:Xenopus laevis
D007473:Ion Channels; D008081:Liposomes; D008563:Membrane Lipids; D011950:Receptors, Cholinergic; D002784:Cholesterol; D006221:Halothane