![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
E Sanna, F Garau and RA Harris
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
In this study we determined the influence of gamma-aminobutyric acid (GABA)A receptor subunit composition on the direct effects of the general anesthetics propofol, pentobarbital, and alphaxalone, using recombinant receptors expressed in Xenopus oocytes. cDNAs coding for human beta 1, alpha 1 beta 1, or alpha 1 beta 1 gamma 2S GABAA receptor subunits were injected into Xenopus oocytes, and responses induced by either GABA or anesthetics were measured by two-electrode voltage-clamp recording. Expression of homomeric beta 1 receptors resulted in the formation of a Cl- channel that was sensitive to picrotoxin and strychnine and could be activated, albeit with relatively low potency, by GABA. However, GABA-induced currents of homomeric beta 1 receptors were completely insensitive to the GABAA receptor antagonist bicuculline. Homomeric beta 1 receptors showed marked direct activation by propofol or pentobarbital, but not by alphaxalone. In contrast, these three anesthetics induced much weaker direct activation of Cl- currents in oocytes expressing alpha 1 beta 1 or alpha 1 beta 1 gamma 2S receptors. These data indicate that the beta 1 subunit of the GABAA receptor forms a functional Cl- channel that contains sites for the direct activating effects of GABA, propofol, and pentobarbital and this GABA site is not blocked by bicuculline.
This article has been cited by other articles:
|
|
 |
|
  J. R. Bracamontes and J. H. Steinbach Multiple Modes for Conferring Surface Expression of Homomeric {beta}1 GABAA Receptors J. Biol. Chem., September 19, 2008; 283(38): 26128 - 26136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Saras, G. Gisselmann, A. K. Vogt-Eisele, K. S. Erlkamp, O. Kletke, H. Pusch, and H. Hatt Histamine Action on Vertebrate GABAA Receptors: DIRECT CHANNEL GATING AND POTENTIATION OF GABA RESPONSES J. Biol. Chem., April 18, 2008; 283(16): 10470 - 10475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kashiwagi, Y. Okada, S.-i. Kuwana, S. Sakuraba, R. Ochiai, and J. Takeda A Neuronal Mechanism of Propofol-Induced Central Respiratory Depression in Newborn Rats Anesth. Analg., July 1, 2004; 99(1): 49 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Miko, E. Werby, H. Sun, J. Healey, and L. Zhang A TM2 Residue in the {beta}1 Subunit Determines Spontaneous Opening of Homomeric and Heteromeric {gamma}-Aminobutyric Acid-gated Ion Channels J. Biol. Chem., May 28, 2004; 279(22): 22833 - 22840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Ekema, W. Zheng, and L. Lu Interaction of GABA Receptor/Channel {rho}1 and {gamma}2 Subunit Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2326 - 2333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Amin A Single Hydrophobic Residue Confers Barbiturate Sensitivity to gamma -Aminobutyric Acid Type C Receptor Mol. Pharmacol., March 1, 1999; 55(3): 411 - 423. [Abstract] [Full Text]
|
|
|
|
|
|
H. R. Vinik, E. L. Bradley Jr., and I. Kissin Isobolographic Analysis of Propofol-Thiopental Hypnotic Interaction in Surgical Patients Anesth. Analg., March 1, 1999; 88(3): 667 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Neelands, J. L. Fisher, M. Bianchi, and R. L. Macdonald Spontaneous and gamma -Aminobutyric Acid (GABA)-Activated GABAA Receptor Channels Formed by epsilon Subunit-Containing Isoforms Mol. Pharmacol., January 1, 1999; 55(1): 168 - 178. [Abstract] [Full Text]
|
|
|
|
|
|
M. D. Krasowski, V. V. Koltchine, C. E. Rick, Q. Ye, S. E. Finn, and N. L. Harrison Propofol and Other Intravenous Anesthetics Have Sites of Action on the gamma -Aminobutyric Acid Type A Receptor Distinct from That for Isoflurane Mol. Pharmacol., March 1, 1998; 53(3): 530 - 538. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. F. Tyndale, S. V. Bhave, E. Hoffmann, P. L. Hoffman, B. Tabakoff, A. J. Tobin, and R. W. Olsen Pentobarbital Decreases the gamma -Aminobutyric AcidA Receptor Subunit gamma-2 Long/Short mRNA Ratio by a Mechanism Distinct from Receptor Occupation J. Pharmacol. Exp. Ther., October 1, 1997; 283(1): 350 - 357. [Abstract] [Full Text]
|
|
|
|
|
|
L. S. Aspinwall, I. Bermudez, L. A. King, and K. A. Wafford The Interactions of Hexachlorocyclohexane Isomers with Human gamma -Aminobutyric AcidA Receptors Expressed in Xenopus Oocytes J. Pharmacol. Exp. Ther., September 1, 1997; 282(3): 1557 - 1564. [Abstract] [Full Text]
|
|
|
|
|
|
E. Sanna, A. Murgia, A. Casula, and G. Biggio Differential Subunit Dependence of the Actions of the General Anesthetics Alphaxalone and Etomidate at gamma -Aminobutyric Acid Type A Receptors Expressed in Xenopus laevis Oocytes Mol. Pharmacol., March 1, 1997; 51(3): 484 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Moore, M. N. Waxham, and P. K. Dash Neuronal Activity Increases the Phosphorylation of the Transcription Factor cAMP Response Element-binding Protein (CREB) in Rat Hippocampus and Cortex J. Biol. Chem., June 14, 1996; 271(24): 14214 - 14220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jenkins, E. P. Greenblatt, H. J. Faulkner, E. Bertaccini, A. Light, A. Lin, A. Andreasen, A. Viner, J. R. Trudell, and N. L. Harrison Evidence for a Common Binding Cavity for Three General Anesthetics within the GABAA Receptor J. Neurosci., March 15, 2001; 21(6): RC136 - RC136. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
