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Differential Effects of Halothane and Isoflurane on Carotid Body Glomus Cell Intracellular Ca2+ and Background K+ Channel Responses to Hypoxia

  • Jaideep J. Pandit
  • Victoria Winter
  • Rebecca Bayliss
  • Keith J. Buckler
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 669)

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 [Ca2+]i (measured using indo-1 dye), halothane and isoflurane (0.45–2.73 MAC) depressed the Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ is also possible.

Keywords

Transient Response Volatile Anaesthetic Hypoxic Response Volatile Agent Glomus Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Buckler, K.J., Williams, B.A., and Honore, E. (2000) An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemo receptor cells. J. Physiol. 525, 135–142.CrossRefPubMedGoogle Scholar
  2. Dolphin, A.C. (2006) A short history of voltage-gated calcium channels. Br. J. Pharmacol. 147(Suppl. 1), S56–S62.PubMedGoogle Scholar
  3. Pandit, J.J. (2002) The variable effect of low-dose volatile anaesthetics on the acute ventilatory response to hypoxia in humans: A quantitative review. Anaesthesia 57, 632-643.CrossRefPubMedGoogle Scholar
  4. Pandit, J.J. (2007) Volatile anesthetics and the hypoxic ventilatory response: Effects, clinical implications, and future research. Sem. Anesth. Periop. Med. Pain 26, 49–57.CrossRefGoogle Scholar
  5. Pandit, J.J. and Buckler, K.J. (2008) Halothane and sevoflurane exert different degree of inhibition on carotid body glomus cell hypoxic response. Anesth. Analg. 16, S-186.Google Scholar
  6. Prabhakar, N. and Overholt, J. (2000) Cellular mechanisms of oxygen sensing at the carotid body: Heme proteins and ion channels. Resp. Phys. 122, 209–221.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jaideep J. Pandit
    • 1
  • Victoria Winter
    • 1
  • Rebecca Bayliss
    • 2
  • Keith J. Buckler
    • 2
  1. 1.Nuffield Department of AnaestheticsJohn Radcliffe HospitalOxfordUK
  2. 2.Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK

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