April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Potentiating Effect of Propofol on GABAA Receptor-Mediated Responses of Retinal Bipolar Cells
Author Affiliations & Notes
  • L. Yue
    Ophthalmology and Visual Sciences,
    University of Illinois at Chicago, Chicago, Illinois
  • A. Xie
    Ophthalmology and Visual Sciences,
    University of Illinois at Chicago, Chicago, Illinois
  • K. S. Bruzik
    Medicinal Chemistry and Pharmacognosy,
    University of Illinois at Chicago, Chicago, Illinois
  • H. Qian
    Ophthalmology and Visual Sciences,
    University of Illinois at Chicago, Chicago, Illinois
  • D. R. Pepperberg
    Ophthalmology and Visual Sciences,
    University of Illinois at Chicago, Chicago, Illinois
  • Footnotes
    Commercial Relationships  L. Yue, None; A. Xie, None; K.S. Bruzik, None; H. Qian, None; D.R. Pepperberg, None.
  • Footnotes
    Support  NIH grants EY016094 and EY001792; Daniel F. and Ada L. Rice Foundation; Hope for Vision; American Health Assistance Foundation; Research to Prevent Blindness
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 1015. doi:
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      L. Yue, A. Xie, K. S. Bruzik, H. Qian, D. R. Pepperberg; Potentiating Effect of Propofol on GABAA Receptor-Mediated Responses of Retinal Bipolar Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1015.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Propofol (2,6-diisopropyl phenol), a widely used anesthetic, is known to modulate the activity of GABAA receptors (e.g., ref. 1) and, in the retina in vivo, to exert an enhancing effect on the electroretinographic (ERG) b-wave (e.g., 2). Retinal bipolar cells are a known locus of GABAA receptors as well as GABAC receptors. As an initial step in studies aimed at constructing and testing receptor-tethered, light-sensitive modulators of bipolar cell GABAA receptors (see, e.g., 3), we have examined the effects of propofol on the GABA response of single, isolated bipolar cells.

Methods: : Whole-cell patch-clamp techniques were used to record membrane current responses from enzymatically dissociated bipolar cells obtained from rat retina. The experiments employed TPMPA and bicuculline as blockers of GABAC and GABAA receptors, respectively.

Results: : TPMPA (100 µM), when co-applied with 10 µM GABA, inhibited the GABA-elicited response by 83 ± 2% (n=10). This mixture of 10 µM GABA plus 100 µM TPMPA (henceforth termed 10G/100T) was used as the nominal condition with which to compare the effects of propofol. When co-applied with 10G/100T, propofol at a concentration of 150 µM increased the response 5.8 ± 2.3 fold (n=6). Increasing concentrations of propofol (5-500 µM) led to a progressive increase in the size of the elicited current response with a half-maximal effect at ~100 µM propofol. When presented alone, 150 µM propofol generated a response comparable with that produced by 10G/100T, consistent with the known modest agonist activity of propofol on the GABAA receptor. The co-application of bicuculline (100 µM) reduced the propofol-enhanced response. Changing the holding potential from -60 mV to -30 mV had no substantial effect on potentiation of the 10G/100T response by propofol (n=2).

Conclusions: : The data indicate that GABAA receptors contribute a minor fraction of the overall response obtained with 10 µM GABA in rat retinal bipolar cells. The present results provide direct evidence for a potentiating action of propofol at these GABAA receptors. After propofol enhancement, the GABAA receptor-mediated response has an amplitude comparable with that mediated by the GABAC receptor on the bipolar cells. Propofol may therefore represent a workable anchoring or effector moiety for light-sensitive GABAA-modulating structures. (1) Bali M & Akabas MH (2004) Molec. Pharmacol. 65:68-76. (2) Kommonen B et al. (2007) Veterinary Ophthalmol. 10:76-80. (3) Volgraf M et al. (2006) Nature Chem Biol. 2:47-52.

Keywords: bipolar cells • neurotransmitters/neurotransmitter systems • ion channels 
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