Differential effects of halothane and sevoflurane on hypoxia-induced intracellular calcium transients of neonatal rat carotid body type I cells.
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 approximately 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.
Pandit
J J
JJ
Nuffield Department of Anaesthetics, John Radcliffe Hospital, Oxford OX3 9DU, UK. jaideep.pandit@dpag.ox.ac.uk
Buckler
K J
KJ
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D008738:Methyl Ethers / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D008738:Methyl Ethers; D000077149:Sevoflurane; D002118:Calcium; D006221:Halothane