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This Article Full Text Full Text (PDF) All Versions of this Article: 96/6/3042    most recent 00571.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map 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 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.

Excitatory and Inhibitory Actions of Isoflurane in Bovine Chromaffin Cells

¹Department of Anesthesia and Critical Care and ²Department of Neurobiology, Pharmacology, and Physiology, The University of Chicago, Chicago, Illinois

Submitted 30 May 2006; accepted in final form 31 August 2006

Isoflurane, a halogenated volatile anesthetic, is thought to produce anesthesia by depressing CNS function. Many anesthetics, including isoflurane, are thought to modulate and/or directly activate GABA_A receptors. Chromaffin cells are known to express functional GABA_A receptors. We previously showed that activation of the GABA_A receptors, with specific agonists, leads to cellular excitation resulting from the depolarized anion equilibrium potential. In this study, our goal was to determine whether isoflurane mimicked this response and to explore the functional consequences of this activation. Furthermore, we sought to study the actions of isoflurane on nicotinic acetylcholine receptors (nAChRs) as they mediate the "sympathetic drive" in these cells. For these studies the Ca²⁺-indicator dye fura-2 was used to assay [Ca²⁺]_i. Amperometric measurements were used to assay catecholamine release. We show that bovine adrenal chromaffin cells were excited by isoflurane at clinically relevant concentrations. Isoflurane directly activated GABA_A receptors found in chromaffin cells, which depolarized the cells and elevated [Ca²⁺]_i. Application of isoflurane directly to the chromaffin cells elicited catecholamine secretion from these cells. At the same time, isoflurane suppressed activation of nAChRs, which presumably blocks "sympathetic drive" to the chromaffin cells. These latter results may help explain why isoflurane produces the hypotension observed clinically.