title: Excitatory and inhibitory actions of isoflurane in bovine chromaffin cells.
abstract: 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 Ca(2+)-indicator dye fura-2 was used to assay [Ca(2+)](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 [Ca(2+)](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.
authors.affiliation: The University of Chicago, Dept. of Anesthesia and Critical Care, 5841 S. Maryland, MC 4028, Chicago, IL 60637, USA. jxie@dacc.uchicago.edu
authors.forename: Z
authors.initials: Z
authors.lastname: Xie
authors.forename: B E
authors.initials: BE
authors.lastname: Herring
authors.forename: A P
authors.initials: AP
authors.lastname: Fox
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005045:Etomidate / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D002395:Catecholamines; D005456:Fluorescent Dyes; D018755:GABA Agonists; D018756:GABA Antagonists; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; D007530:Isoflurane; D002118:Calcium; D016257:Fura-2; D001640:Bicuculline; D005045:Etomidate