May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Toward Development of Neurotransmitter- Derivatized Surfaces for Interaction with Post-Synaptic Membrane Receptors
Author Affiliations & Notes
  • T.Q. Vu
    Oph & Vis Sci, U Illinois, Chicago, IL, United States
  • H. Qian
    Oph & Vis Sci, U Illinois, Chicago, IL, United States
  • U. Saifuddin
    Bioeng, U Illinois, Chicago, IL, United States
  • M. Rezac
    Med Chem & Pharm, U Illinois, Chicago, IL, United States
  • T.A. Desai
    Biomed Eng, Boston U, Boston, MA, United States
  • D.R. Pepperberg
    Biomed Eng, Boston U, Boston, MA, United States
  • Footnotes
    Commercial Relationships  T.Q. Vu, None; H. Qian, None; U. Saifuddin, None; M. Rezac, None; T.A. Desai, None; D.R. Pepperberg, None.
  • Footnotes
    Support  NIH EY13693 and Univ. of Illinois IRIB Program
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1064. doi:
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      T.Q. Vu, H. Qian, U. Saifuddin, M. Rezac, T.A. Desai, D.R. Pepperberg; Toward Development of Neurotransmitter- Derivatized Surfaces for Interaction with Post-Synaptic Membrane Receptors . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1064.

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

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Abstract

Abstract: : Purpose: Synaptic neurotransmission involves the stimulus-controlled release of neurotransmitter by pre-synaptic neurons and its subsequent binding to post-synaptic membrane receptors. In certain retinal degenerative diseases, pre-synaptic neuronal function is compromised while post-synaptic function appears to be preserved. A possible approach to restoring activity at these inactive synapses is to develop submicroscopic platforms that can interface specifically with the post-synaptic membrane and in controlled fashion present a functional, tethered neurotransmitter analog to post-synaptic receptors. As initial steps towards this goal, we have studied properties of surface-tethered and solubilized derivatives of GABA, a major retinal neurotransmitter. Methods: Functionality of solubilized GABA derivatives was examined in Xenopus oocytes expressing either GABAA or GABAC receptors (two-electrode voltage clamp recording). GABA-tethered surfaces were assembled using passive adsorption of avidin to mica and attachment of a biotinylated analog of GABA. Surfaces were visualized with atomic force microscopy (AFM). Surface bioactivity was tested with anti-GABA antibody (1). Results: Among compounds tested electrophysiologically, an N-substituted derivative of muscimol terminated by a BODIPY fluorescent group elicited chloride currents from oocytes expressing either GABAA or GABAC receptors. Amplitudues of responses to 10 µM muscimol-BODIPY were comparable to those elicited by 10 µM GABA. Bicuculline (100 µM) blocked these responses in GABAA but not in GABAC receptors. While muscimol-BODIPY was not tethered to a surface, we have synthesized and tested an N-substituted GABA analog containing a terminating biotin group, tethered by attachment to avidin adsorbed on a solid substrate. By AFM, surfaces containing biotinylated GABA showed distinct morphologies controllable by avidin concentration. Biotinylated GABA showed little if any activity in oocytes expressing GABAA or GABAC receptors. However, surfaces containing this compound exhibited specific affinity for anti-GABA antibody and in this regard were biofunctional (1). Conclusions: These results describe a prototype approach for preparing chain-derivatized neurotransmitter analogs that exhibit biological activity and can be attached to a supporting surface. The data motivate further work aimed at constructing immobilized neurotransmitter analogs that can interact with post-synaptic receptors. (1) Saifuddin et al., J. Biomed. Mater. Res., in press.

Keywords: retina • neurotransmitters/neurotransmitter systems • synapse 
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