| Robust photoregulation of GABA(A) receptors by allosteric modulation with a propofol analogue. | |
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MedLine Citation:
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PMID: 23033071 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Photochemical switches represent a powerful method for improving pharmacological therapies and controlling cellular physiology. Here we report the photoregulation of GABA(A) receptors (GABA(A)Rs) by a derivative of propofol (2,6-diisopropylphenol), a GABA(A)R allosteric modulator, which we have modified to contain photoisomerizable azobenzene. Using α(1)β(2)γ(2) GABA(A)Rs expressed in Xenopus laevis oocytes and native GABA(A)Rs of isolated retinal ganglion cells, we show that the trans-azobenzene isomer of the new compound (trans-MPC088), generated by visible light (wavelengths ~440 nm), potentiates the γ-aminobutyric acid-elicited response and, at higher concentrations, directly activates the receptors. cis-MPC088, generated from trans-MPC088 by ultraviolet light (~365 nm), produces little, if any, receptor potentiation/activation. In cerebellar slices, MPC088 co-applied with γ-aminobutyric acid affords bidirectional photomodulation of Purkinje cell membrane current and spike-firing rate. The findings demonstrate photocontrol of GABA(A)Rs by an allosteric ligand, and open new avenues for fundamental and clinically oriented research on GABA(A)Rs, a major class of neurotransmitter receptors in the central nervous system. |
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Authors:
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Lan Yue; Michal Pawlowski; Shlomo S Dellal; An Xie; Feng Feng; Thomas S Otis; Karol S Bruzik; Haohua Qian; David R Pepperberg |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Nature communications Volume: 3 ISSN: 2041-1723 ISO Abbreviation: Nat Commun Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-03 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101528555 Medline TA: Nat Commun Country: England |
Other Details:
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Languages: eng Pagination: 1095 Citation Subset: IM |
Affiliation:
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1] Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, Illinois 60612, USA. [2] Department of Bioengineering, University of Illinois at Chicago, 851 South Morgan Street, Chicago, Illinois 60607, USA. [3]. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PubChem-Substance/144100999; 144101000; 144101001 |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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