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BJA Advance Access originally published online on August 21, 2009
British Journal of Anaesthesia 2009 103(5):701-710; doi:10.1093/bja/aep223
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© The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Differential effects of halothane and sevoflurane on hypoxia-induced intracellular calcium transients of neonatal rat carotid body type I cells{dagger}

J. J. Pandit1,* and K. J. Buckler2

1 Nuffield Department of Anaesthetics, John Radcliffe Hospital, Oxford OX3 9DU, UK and
2 Department of Anatomy, Physiology and Genetics, Parks Road, Oxford OX1 3PT, UK

* Corresponding author. E-mail: jaideep.pandit{at}dpag.ox.ac.uk

Background: The purpose of this study was to investigate the effects of halothane and sevoflurane on the magnitude of the increase in intracellular calcium with hypoxia in carotid body type I (glomus) cells. We wished to ascertain if the effects of these agents in single cells paralleled their known effects on the human hypoxic ventilatory response, where halothane depresses this response more than does sevoflurane.

Methods: We studied single glomus cells from neonatal rat carotid bodies. Halothane and sevoflurane were administered in concentrations ranging from 0.18 to 1.45 and 0.1 to 2 minimum alveolar concentration (MAC), respectively (rat values). The intracellular calcium response to a ~90 s period of hypoxia was measured using indo-1 dye. We also assessed if these agents influenced the calcium response to exposure to potassium 100 mM.

Results: Halothane depressed the increase in intracellular calcium with hypoxia more than did sevoflurane (P=0.036). Although halothane was depressive at all concentrations tested, sevoflurane depressed the calcium response only at 2 MAC. Both agents also depressed the calcium response to elevated extracellular potassium—halothane more so than sevoflurane (P=0.004).

Conclusions: The actions of the agents in single cells reflect their known influence on human hypoxic ventilatory response, consistent with the notion that the cellular process underlies the whole-body effect. The responses to elevated extracellular potassium, which depolarizes the cell membrane, indicate that (in addition to molecular mechanisms previously proposed), voltage-activated calcium channels may also be involved in the anaesthetic effect.

Keywords: chemoreflexes; ions, ion channels; receptors, chemoreceptors, carotid body; ventilation, hypoxic response


{dagger} This work was presented in part at the 82nd Annual Meeting of the International Anesthetic Research Society, San Francisco, CA, USA, March 29–April 1, 2008.


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