QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 29, 2004, 24(39):8454-8458; doi:10.1523/JNEUROSCI.2063-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science 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 Web of Science (50) Citing Articles via Google Scholar Google Scholar Articles by Caraiscos, V. B. Articles by Orser, B. A. Search for Related Content PubMed PubMed Citation Articles by Caraiscos, V. B. Articles by Orser, B. A.

 Previous Article  |  Next Article 

BRIEF COMMUNICATION
Selective Enhancement of Tonic GABAergic Inhibition in Murine Hippocampal Neurons by Low Concentrations of the Volatile Anesthetic Isoflurane

Valerie B. Caraiscos,¹ J. Glen Newell,³ Kong E. You-Ten,² Erin M. Elliott,¹ Thomas W. Rosahl,⁵ Keith A. Wafford,⁵ John F. MacDonald,^3,4 and Beverley A. Orser^1,2,3,6

¹Institute of Medical Science, Departments of ²Anesthesia, ³Physiology, and ⁴Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 1A8, Canada, ⁵Merck Sharp and Dohme Research Laboratories, Neuroscience Research Center, Terlings Park, Harlow, Essex CM20 2QR, United Kingdom, and ⁶Department of Anesthesia, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada

Volatile (inhaled) anesthetics cause amnesia at concentrations well below those that cause loss of consciousness and immobility; however, the underlying neuronal mechanisms are unknown. Although many anesthetics increase inhibitory GABAergic synaptic transmission, this effect occurs only at high concentrations (>100 µM). Molecular targets for low concentrations of inhaled anesthetics have not been identified. Here, we report that a tonic inhibitory conductance in hippocampal pyramidal neurons generated by 5 subunit-containing GABA_A receptors is highly sensitive to low concentrations of the volatile anesthetic isoflurane (ISO) (25 and 83.3 µM). The 5 subunit is necessary for enhancement of the tonic current by these low concentrations of isoflurane because potentiation is absent in neurons from 5^-/- mice. Furthermore, ISO (25 µM) potentiated recombinant human 532L GABA_A receptors, whereas this effect was not seen with 132L GABA_A receptors. These studies suggest that an increased tonic inhibition in the hippocampus may contribute to amnestic properties of volatile anesthetics.

Key words: amnesia; anesthesia; GABA; extrasynaptic; 5 subunit; heterologous expression

---

Received May 27, 2004; revised August 9, 2004; accepted August 10, 2004.

This article has been cited by other articles:

				V. Rau, S. V. Iyer, I. Oh, D. Chandra, N. Harrison, E. I. Eger II, M. S. Fanselow, G. E. Homanics, and J. M. Sonner Gamma-Aminobutyric Acid Type A Receptor Alpha 4 Subunit Knockout Mice Are Resistant to the Amnestic Effect of Isoflurane Anesth. Analg., December 1, 2009; 109(6): 1816 - 1822. [Abstract] [Full Text] [PDF]

				D. Belelli, N. L. Harrison, J. Maguire, R. L. Macdonald, M. C. Walker, and D. W. Cope Extrasynaptic GABAA Receptors: Form, Pharmacology, and Function J. Neurosci., October 14, 2009; 29(41): 12757 - 12763. [Abstract] [Full Text] [PDF]

				J. Liang, I. Spigelman, and R. W. Olsen Tolerance to Sedative/Hypnotic Actions of GABAergic Drugs Correlates With Tolerance to Potentiation of Extrasynaptic Tonic Currents of Alcohol-Dependent Rats J Neurophysiol, July 1, 2009; 102(1): 224 - 233. [Abstract] [Full Text] [PDF]

				M. C. Bieda, H. Su, and M. B. MacIver Anesthetics Discriminate Between Tonic and Phasic {gamma}-Aminobutyric Acid Receptors on Hippocampal CA1 Neurons Anesth. Analg., February 1, 2009; 108(2): 484 - 490. [Abstract] [Full Text] [PDF]

				X. Wang Propofol and Isoflurane Enhancement of Tonic Gamma-Aminobutyric Acid Type A Current in Cardiac Vagal Neurons in the Nucleus Ambiguus Anesth. Analg., January 1, 2009; 108(1): 142 - 148. [Abstract] [Full Text] [PDF]

				S. Rex, P. T. Meyer, J.-H. Baumert, R. Rossaint, M. Fries, U. Bull, and W. M. Schaefer Positron emission tomography study of regional cerebral blood flow and flow-metabolism coupling during general anaesthesia with xenon in humans Br. J. Anaesth., May 1, 2008; 100(5): 667 - 675. [Abstract] [Full Text] [PDF]

				B. A. Orser Depth-of-Anesthesia Monitor and the Frequency of Intraoperative Awareness N. Engl. J. Med., March 13, 2008; 358(11): 1189 - 1191. [Full Text] [PDF]

				F. Jia, M. Yue, D. Chandra, G. E. Homanics, P. A. Goldstein, and N. L. Harrison Isoflurane Is a Potent Modulator of Extrasynaptic GABAA Receptors in the Thalamus J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1127 - 1135. [Abstract] [Full Text] [PDF]

				R. P. Bonin, L. J. Martin, J. F. MacDonald, and B. A. Orser {alpha}5GABAA Receptors Regulate the Intrinsic Excitability of Mouse Hippocampal Pyramidal Neurons J Neurophysiol, October 1, 2007; 98(4): 2244 - 2254. [Abstract] [Full Text] [PDF]

				D. Chandra, F. Jia, J. Liang, Z. Peng, A. Suryanarayanan, D. F. Werner, I. Spigelman, C. R. Houser, R. W. Olsen, N. L. Harrison, et al. GABAA receptor {alpha}4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol PNAS, October 10, 2006; 103(41): 15230 - 15235. [Abstract] [Full Text] [PDF]

				M. Yamashita, W. Marszalec, J. Z. Yeh, and T. Narahashi Effects of Ethanol on Tonic GABA Currents in Cerebellar Granule Cells and Mammalian Cells Recombinantly Expressing GABAA Receptors J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 431 - 438. [Abstract] [Full Text] [PDF]

				G. A. Prenosil, E. M. Schneider Gasser, U. Rudolph, R. Keist, J.-M. Fritschy, and K. E. Vogt Specific Subtypes of GABAA Receptors Mediate Phasic and Tonic Forms of Inhibition in Hippocampal Pyramidal Neurons J Neurophysiol, August 1, 2006; 96(2): 846 - 857. [Abstract] [Full Text] [PDF]

				K. R. Drasbek and K. Jensen THIP, a Hypnotic and Antinociceptive Drug, Enhances an Extrasynaptic GABAA Receptor-mediated Conductance in Mouse Neocortex Cereb Cortex, August 1, 2006; 16(8): 1134 - 1141. [Abstract] [Full Text] [PDF]

				V. Y. Cheng, L. J. Martin, E. M. Elliott, J. H. Kim, H. T. J. Mount, F. A. Taverna, J. C. Roder, J. F. MacDonald, A. Bhambri, N. Collinson, et al. Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate. J. Neurosci., April 5, 2006; 26(14): 3713 - 3720. [Abstract] [Full Text] [PDF]

				J. Liang, N. Zhang, E. Cagetti, C. R. Houser, R. W. Olsen, and I. Spigelman Chronic Intermittent Ethanol-Induced Switch of Ethanol Actions from Extrasynaptic to Synaptic Hippocampal GABAA Receptors J. Neurosci., February 8, 2006; 26(6): 1749 - 1758. [Abstract] [Full Text] [PDF]

				J. Engelmann, J. Bacelo, E. van den Burg, and K. Grant Sensory and Motor Effects of Etomidate Anesthesia J Neurophysiol, February 1, 2006; 95(2): 1231 - 1243. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help