JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

Anesth Analg 2009; 108:142-148
© 2009 International Anesthesia Research Society
doi: 10.1213/ane.0b013e31818d8b79
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, X.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, X.
Related Collections
Right arrow Cardiovascular
Right arrow Mechanisms
Right arrow Heart
Right arrow Preclinical Pharmacology
Right arrow Pharmacology

ANESTHETIC PHARMACOLOGY

Propofol and Isoflurane Enhancement of Tonic Gamma-Aminobutyric Acid Type A Current in Cardiac Vagal Neurons in the Nucleus Ambiguus

Xin Wang, PhD, MD

From the Department of Pharmacology and Physiology, and Department of Anesthesiology and Critical Care Medicine, The George Washington University, Washington DC.

Address correspondence and reprint requests to Xin Wang, PhD, MD, Department of Pharmacology and Physiology, and Department of Anesthesiology and Critical Care Medicine, The George Washington University, 2300 Eye Street NW, Ross Hall 654, Washington, DC, 20037. Address e-mail to xinwang{at}gwu.edu.

BACKGROUND: General anesthesia with propofol and isoflurane induces alterations of the cardiovascular system, including hypotension and changes in heart rate. The preganglionic cardiac vagal neurons (CVNs) are one of the major central components controlling heart rate and autonomic regulation. In this study, we examined whether propofol and isoflurane act on phasic or tonic {gamma}-aminobutyric acid type A (GABAA) receptor-mediated inhibition in CVNs.

METHODS: CVNs were identified in vitro by retrograde fluorescent labeling. Phasic and tonic GABA currents in CVNs were examined using the whole cell patch-clamp technique.

RESULTS: Propofol (10 µM) increased the membrane holding currents by 63 ± 13% and prolonged the decay time of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) from 42.3 ± 2.8 ms in control to 61.8 ± 4.5 ms. Isoflurane, at concentrations of 100, 300, and 500 µM, decreased GABAergic mIPSCs frequency by 26.0 ± 16%, 64.6 ± 10.4%, and 70.5 ± 9.8%, prolonged the decay time of GABAergic mIPSCs from 47.9 ± 7.3 to 64.5 ± 8.1 ms, 70.3 ± 10.4 ms, and 66.8 ± 8.1 ms, and increased the membrane holding currents by 32.8 ± 12.8%, 42.7 ± 10%, and 39.9 ± 3%, respectively. The GABAergic antagonist gabazine (25 µM) blocked GABAergic mIPSCs, but failed to alter the enhanced holding potential induced by propofol and isoflurane. In contrast, the channel blocker of GABAA receptors, picrotoxin (100 µM), reversed the propofol and isoflurane-evoked increase in membrane holding current.

CONCLUSION: The results demonstrate that the general anesthetics propofol and isoflurane enhance both phasic and tonic GABAA receptor-mediated inhibition of CVNs.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2009 by the International Anesthesia Research Society.