Protons inhibit Cl− conductance by direct or allosteric interaction with the GABA-binding site in the rat recombinant α1β2γ2L and α1β2 GABAA receptor

2005 ◽  
Vol 528 (1-3) ◽  
pp. 1-6 ◽  
Author(s):  
Ming-De Wang ◽  
Mozibur Rahman ◽  
Di Zhu
Keyword(s):  
Binding Site ◽  
Gabaa Receptor ◽  
Allosteric Interaction ◽  
Gaba Binding ◽  
Cl Conductance

Identification of amino acid residues responsible for the α5  subunit binding selectivity of L-655,708, a benzodiazepine binding site ligand at the GABAA receptor

2001 ◽  
Vol 77 (2) ◽  
pp. 445-451 ◽  
Author(s):  
M. Anna Casula ◽  
Frances A. Bromidge ◽  
Gopalan V. Pillai ◽  
Peter B. Wingrove ◽  
Karine Martin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Binding Site ◽  
Gabaa Receptor ◽  
Amino Acid Residues ◽  
Binding Selectivity ◽  
Benzodiazepine Binding

scholarly journals Ligands of the GABAA Receptor Benzodiazepine Binding Site

2006 ◽  
Vol 5 (2) ◽  
pp. 125-144 ◽  
Author(s):  
Qinmi Wang ◽  
Yifan Han ◽  
Hong Xue
Keyword(s):  
Binding Site ◽  
Gabaa Receptor ◽  
Benzodiazepine Binding

scholarly journals Mouse Bestrophin-2 Is a Bona fide Cl− Channel

2004 ◽  
Vol 123 (4) ◽  
pp. 327-340 ◽  
Author(s):  
Zhiqiang Qu ◽  
Rodolphe Fischmeister ◽  
Criss Hartzell
Keyword(s):  
Binding Site ◽  
Cell Lines ◽  
Electrostatic Interactions ◽  
Anion Binding ◽  
Wild Type ◽  
Cl Channel ◽  
Mammalian Cell Lines ◽  
Conduction Pathway ◽  
Bona Fide ◽  
Cl Conductance

Bestrophins have recently been proposed to comprise a new family of Cl− channels. Our goal was to test whether mouse bestrophin-2 (mBest2) is a bona fide Cl− channel. We expressed mBest2 in three different mammalian cell lines. mBest2 was trafficked to the plasma membrane as shown by biotinylation and immunoprecipitation, and induced a Ca2+-activated Cl− current in all three cell lines (EC50 for Ca2+ = 230 nM). The permeability sequence was SCN−: I−: Br−: Cl−: F− (8.2: 1.9: 1.4: 1: 0.5). Although SCN− was highly permeant, its conductance was ∼10% that of Cl− and SCN− blocked Cl− conductance (IC50 = 12 mM). Therefore, SCN− entered the pore more easily than Cl−, but bound more tightly than Cl−. Mutations in S79 altered the relative permeability and conductance for SCN− as expected if S79 contributed to an anion binding site in the channel. PSCN/PCl = 8.2 ± 1.3 for wild-type and 3.9 ± 0.4 for S79C. GSCN/GCl = 0.14 ± 0.03 for wild-type and 0.94 ± 0.04 for S79C. In the S79 mutants, SCN− did not block Cl− conductance. This suggested that the S79C mutation altered the affinity of an anion binding site for SCN−. Additional evidence that S79 was located in the conduction pathway was provided by the finding that modification of the sulfhydryl group in S79C with MTSET+ or MTSES− increased conductance significantly. Because the effect of positively and negatively charged MTS reagents was similar, electrostatic interactions between the permeant anion and the channel at this residue were probably not critical in anion selectivity. These data provide strong evidence that mBest2 forms part of the novel Cl− conduction pathway in mBest2-transfected cells and that S79 plays an important role in anion binding in the pore of the channel.

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