Hydrophobic residue in GABAA receptor ligand binding site strongly influences receptor gating

• Autorzy: Szczot M. , Kisiel M. , Czyzewska M. M. , Mozrzymas J. W.
• Języki publikacji: EN

Abstrakty

EN

Despite broad knowledge on GABAA receptors (GABAARs) structure, the mechanism of ligand induced conformational transitions remains poorly understood. To address this issue we have examined the activity of a recombinant α1/β1/γ2 GABAAR with point mutation introduced at the ligand binding site. Currents were elicited by ultrafast GABA applications and measured using patch-clamp technique. We show that cystein mutation of single hydrophobic residue not only weakened the agonist binding but also abolished fast desensitization and slowed the onset of currents evoked by saturating GABA. Non-stationary variance analysis showed that the mutation does not affect single channel conductance, but reduces maximal open probability, further indicating a change in gating properties. Ratio of current amplitudes elicited by pentobarbital (which activates GABAAR by different pathway than GABA), and by GABA was higher for mutant receptors, supporting interference with receptor gating. Our data show that the considered residue may strongly influence conformational transitions of GABAARs thus indicating this residue as a key element in transduction of free energy supplied by agonist binding to the conformational transitions.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2012
• Tom: 72
• Numer: 2
• Opis fizyczny: p.200

Twórcy

autor

Szczot M.

• Laboratory of Nuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Kisiel M.

• Laboratory of Nuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Czyzewska M. M.

• Laboratory of Nuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Mozrzymas J. W.

• Laboratory of Nuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland
• Department of Animal Molecular Physiology, Institute of Zoology, Wroclaw University, Wroclaw, Poland

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