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

This Article Full Text Full Text (PDF) All Versions of this Article: mol.104.003426v1 66/6/1517    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Feng, H.-J. Articles by Macdonald, R. L. Search for Related Content PubMed PubMed Citation Articles by Feng, H.-J. Articles by Macdonald, R. L.

Multiple Actions of Propofol on and GABA_A Receptors

Departments of Neurology (H.-J.F., R.L.M.), Molecular Physiology and Biophysics (R.L.M.), and Pharmacology (R.L.M.), Vanderbilt University Medical Center, Nashville, Tennessee

GABA_A receptors are predominantly composed of and isoforms in the brain. It has been proposed that receptors mediate phasic inhibition, whereas receptors mediate tonic inhibition. Propofol (2,6-di-isopropylphenol), a widely used anesthetic drug, exerts its effect primarily by modulating GABA_A receptors; however, the effects of propofol on the kinetic properties of and receptors are uncertain. We transfected human embryonic kidney (HEK293T) cells with cDNAs encoding rat 1, 6, 3, 2L, or subunits and performed whole-cell patch-clamp recordings to explore this issue. Propofol (3 µM) increased GABA concentration-response curve maximal currents similarly for both 132L and 632L receptors, but propofol increased those for 13 and 63 receptors differently, the increase being greater for 13 than for 63 receptors. Propofol (10 µM) produced similar alterations in 132L and 632L receptor currents when using a preapplication protocol; peak currents were not altered, desensitization was reduced, and deactivation was prolonged. Propofol enhanced peak currents for both 13 and 63 receptors, but the enhancement was greater for 13 receptors. Desensitization of these two isoforms was not modified by propofol. Propofol did not alter the deactivation rate of 13 receptor currents but did slow deactivation of 63 receptor currents. The findings that propofol reduced desensitization and prolonged deactivation of 2L subunit-containing receptors and enhanced peak currents or prolonged deactivation of subunit-containing receptors suggest that propofol enhancement of both phasic and tonic inhibition may contribute to its anesthetic effect in the brain.

Address correspondence to: Dr. Robert L. Macdonald, Department of Neurology, Vanderbilt University Medical Center, 6140 Medical Research Building III, 465 21st Ave., South, Nashville, Tennessee 37232-8552. E-mail: robert.macdonald{at}vanderbilt.edu

This article has been cited by other articles:

				H. P. Goodkin, S. Joshi, Z. Mtchedlishvili, J. Brar, and J. Kapur Subunit-Specific Trafficking of GABAA Receptors during Status Epilepticus J. Neurosci., March 5, 2008; 28(10): 2527 - 2538. [Abstract] [Full Text] [PDF]

				C. J. Herden, N. E. Pardo, R. K. Hajela, Y. Yuan, and W. D. Atchison Differential Effects of Methylmercury on {gamma}-Aminobutyric Acid Type A Receptor Currents in Rat Cerebellar Granule and Cerebral Cortical Neurons in Culture J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 517 - 528. [Abstract] [Full Text] [PDF]

				M. T. Bianchi, E. J. Botzolakis, K. F. Haas, J. L. Fisher, and R. L. Macdonald Microscopic kinetic determinants of macroscopic currents: insights from coupling and uncoupling of GABAA receptor desensitization and deactivation J. Physiol., November 1, 2007; 584(3): 769 - 787. [Abstract] [Full Text] [PDF]

				M. Mortensen and T. G. Smart Extrasynaptic {alpha}{beta} subunit GABAA receptors on rat hippocampal pyramidal neurons J. Physiol., December 15, 2006; 577(3): 841 - 856. [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]

				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]

				I. Yamaoka, M. Doi, M. Nakayama, A. Ozeki, S. Mochizuki, K. Sugahara, and F. Yoshizawa Intravenous administration of amino acids during anesthesia stimulates muscle protein synthesis and heat accumulation in the body Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E882 - E888. [Abstract] [Full Text] [PDF]

				D. A. Wagner, M. P. Goldschen-Ohm, T. G. Hales, and M. V. Jones Kinetics and Spontaneous Open Probability Conferred by the {epsilon} Subunit of the GABAA Receptor J. Neurosci., November 9, 2005; 25(45): 10462 - 10468. [Abstract] [Full Text] [PDF]