title: Halothane acts on many potassium channels, including a minimal potassium channel.
abstract: There has been considerable controversy over whether general anesthetics act directly on membrane proteins, and if so, whether there are uniquely sensitive protein targets upon which they act. Here, we examine the actions of halothane on a diverse collection of voltage-gated potassium channels expressed in Xenopus oocytes, and find that they are all sensitive at clinically relevant concentrations. To investigate further the molecular basis of this commonality, human and rat minimal potassium (minK) channels, which have exceedingly short amino acid sequences, were examined. Current through these channels is reversibly reduced to 68% of control values by 0.5% (0.34 mM) halothane. A double deletion mutant of the 130-amino acid minK protein, in which 30 amino acids of the N-terminus, thought to be extracellular, and 37 amino acids of the putative intracellular C-terminus are deleted (resulting in a protein in which more than half of both the extracellular and intracellular domains have been removed) responds to low halothane concentrations similarly to the parent channel. While alternative explanations are possible, this result is consistent with a model whereby halothane interacts with the channel protein from within the lipid bilayer.
authors.affiliation: Department of Pharmacology, University of Massachusetts Medical Center, Worcester 01655.
authors.forename: L
authors.initials: L
authors.lastname: Zorn
authors.forename: R
authors.initials: R
authors.lastname: Kulkarni
authors.forename: V
authors.initials: V
authors.lastname: Anantharam
authors.forename: H
authors.initials: H
authors.lastname: Bayley
authors.forename: S N
authors.initials: SN
authors.lastname: Treistman
mesh_terms: D000818:Animals; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D014981:Xenopus
chemical_list: D015221:Potassium Channels; D006221:Halothane