title: Differential effects of halothane and isoflurane on carotid body glomus cell intracellular Ca2+ and background K+ channel responses to hypoxia.
abstract: We recently reported that volatile anaesthetics directly depress the isolated glomus cell response to hypoxia, halothane more so than sevoflurane, in a manner mimicking the action of these agents on the human hypoxic ventilatory response. We wished to extend these investigations to action of another agent (isoflurane), and we planned to examine the effects of this agent and halothane on background K(+) channels. In an isolated rat pup glomus cell preparation intracellular calcium [Ca(2+)]i (measured using indo-1 dye), halothane and isoflurane (0.45-2.73 MAC) depressed the Ca(2+) transient response to hypoxia (p = 0.028), halothane more than isoflurane (p < 0.001). Evaluating the effects of halothane, isoflurane (both 2.5 MAC) and hypoxia on the open probability of background TASK-like K(+) channels in cell attached patch recordings, halothane in euoxia strongly increased channel activity (2 fold) but isoflurane only increased activity by 50% (p < 0.001). In the presence of hypoxia halothane also increased channel activity (3 fold) while isoflurane again only had weak effects (p = 0.004). Thus there were marked differences between these agents on K(+) channel activity, comparable to their effects on the hypoxia induced Ca(2+) transient. When glomus cells were exposed to a depolarising stimulus using 100 mM K(+), both halothane and isoflurane modestly reduced the magnitude of the resulting Ca(2+) transient (by 44% and 10% respectively, p < 0.001). We conclude that the effect of volatile anaesthetics on the glomus cell response to hypoxia is mediated at least in part by their effect on background K(+) channels, and that this plausibly explains their whole-body effect. An additional effect on voltage-gated Ca(2+) is also possible.
authors.affiliation: Nuffield Department of Anaesthetics, John Radcliffe Hospital, Oxford, UK. jaideep.pandit@dpag.ox.ac.uk
authors.forename: Jaideep J
authors.initials: JJ
authors.lastname: Pandit
authors.forename: Victoria
authors.initials: V
authors.lastname: Winter
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bayliss
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Buckler
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002344:Carotid Body / Q000166:cytology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects* / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015221:Potassium Channels; D007530:Isoflurane; D002118:Calcium; D006221:Halothane