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This Article Full Text Full Text (PDF) All Versions of this Article: 560/3/677    most recent jphysiol.2004.070664v2 jphysiol.2004.070664v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xie, Z Articles by Fox, A. P Search for Related Content PubMed PubMed Citation Articles by Xie, Z Articles by Fox, A. P

¹ University of Chicago, Department of Anesthesia and Critical Care, 5841 S. Maryland, MC 4028, Chicago, IL 60637, USA
² Department of Neurobiology, Pharmacology and Physiology, 947 E. 58th Street, Chicago, IL 60637, USA

Etomidate, an intravenous imidazole general anaesthetic, is thought to produce anaesthesia by modulating or activating ionotropic Cl^–-permeable GABA_A receptors. Chromaffin cells are known to express functional GABA_A receptors with properties similar to their neuronal counterparts. We have shown that activation of the GABA_A receptors, with specific GABA_A agonists, leads to cellular excitation. Our goal was to determine whether etomidate mimicked this response and to explore the functional consequences of this activation. Imaging experiments with the Ca²⁺-indicator dye fura-2 were used to assay [Ca²⁺]_i. Bovine adrenal chromaffin cells were superfused with a variety of GABA_A-selective drugs to determine their effects on [Ca²⁺]_i. Amperometric measurements were used to assay catecholamine release in real-time. We show that bovine adrenal chromaffin cells were excited by etomidate at clinically relevant concentrations. Etomidate directly activated GABA_A receptors found in chromaffin cells thereby elevating [Ca²⁺]_i. The effects of etomidate were mimicked by the specific GABA_A agonist muscimol and blocked by the specific antagonist bicuculline. Our data show that low concentrations of etomidate modulated GABA_A receptor activation by muscimol. Blockade of voltage-dependent Ca²⁺ channels prevented the elevation of [Ca²⁺]_i by GABA. Application of etomidate directly to the chromaffin cells elicited robust catecholamine secretion from these cells. The data indicate that clinically relevant concentrations of etomidate can directly activate GABA_A receptors, which, due to the positive anion equilibrium potential, depolarizes chromaffin cells. This depolarization activates voltage-dependent Ca²⁺ channels thereby stimulating catecholamine release. Our data suggest that circulating catecholamine levels may be elevated after etomidate application.

(Received 25 June 2004; accepted after revision 23 August 2004; first published online 26 August 2004)
Corresponding author Z. Xie: University of Chicago, Department of Anesthesia and Critical Care, 5841 S. Maryland; MC 4028, Chicago, IL 60637, USA. Email: jxie{at}airway.bsd.uchicago.edu

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