Etomidate elevates intracellular calcium levels and promotes catecholamine secretion in bovine chromaffin cells

Z. Xie, K. P.M. Currie, A. P. Fox

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Etomidate, an intravenous imidazole general anaesthetic, is thought to produce anaesthesia by modulating or activating ionotropic Cl-permeable GABAA receptors. Chromaffin cells are known to express functional GABAA receptors with properties similar to their neuronal counterparts. We have shown that activation of the GABAA receptors, with specific GABAA 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 GABAA-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 GABAA receptors found in chromaffin cells thereby elevating [Ca2+]i. The effects of etomidate were mimicked by the specific GABAA agonist muscimol and blocked by the specific antagonist bicuculline. Our data show that low concentrations of etomidate modulated GABAA receptor activation by muscimol. Blockade of voltage-dependent Ca2+ channels prevented the elevation of [Ca+2+]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 GABAA receptors, which, due to the positive anion equilibrium potential, depolarizes chromaffin cells. This depolarization activates voltage-dependent Ca+2+ channels thereby stimulating catecholamine release. Our data suggest that circulating catecholamine levels may be elevated after etomidate application.

Original languageEnglish (US)
Pages (from-to)677-690
Number of pages14
JournalJournal of Physiology
Volume560
Issue number3
DOIs
StatePublished - Nov 1 2004

All Science Journal Classification (ASJC) codes

  • Physiology

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