Document Detail

Robust photoregulation of GABA(A) receptors by allosteric modulation with a propofol analogue.
MedLine Citation:
PMID:  23033071     Owner:  NLM     Status:  In-Data-Review    
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.
Lan Yue; Michal Pawlowski; Shlomo S Dellal; An Xie; Feng Feng; Thomas S Otis; Karol S Bruzik; Haohua Qian; David R Pepperberg
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature communications     Volume:  3     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  1095     Citation Subset:  IM    
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.:
PubChem-Substance/144100999;  144101000;  144101001
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