Alpha1F64 influences GABAAR gating through flipping mechanism

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

Abstrakty

EN

GABAARs are crucial for neuronal inhibition. Using patch-clamp technique with ultrafast perfusion we found that mutations of hydrophobic residue at GABA-binding site affected not only binding affinity but also kinetics of macroscopic desensitization. Nonstationary variance analysis indicated that α1F64C mutation reduces maximum open probability. To obtain further information about the role of α1F64 we used two different agonists. Experiments with a partial agonist, P4S, suggested an impact of α1F64C mutation on the channel gating efficacy. Application of muscimol (with higher affinity than GABA) entailed a partial rescue of rapid desensitization in α1F64Lβ1γ2 receptors but in cysteine mutants – did not. Model simulations show that observed effects result from changes in flipping mechanism which links binding and gating. We conclude that α1F64 plays a crucial role in signal transduction from binding site to the channel gate. Supported by NCN Grant 350/B/P01/2011/40 to JWM

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2014
• Tom: 74
• Numer: 3
• Opis fizyczny: p.332

Twórcy

autor

Kisiel M.

• Laboratory of Neuroscience, Department of Biophysics, Wrocław Medical University, Wrocław, Poland

autor

Szczot M.

• Laboratory of Neuroscience, Department of Biophysics, Wrocław Medical University, Wrocław, Poland

autor

Czyzewska M. M.

• Laboratory of Neuroscience, Department of Biophysics, Wrocław Medical University, Wrocław, Poland

autor

Jatczak M.

• Laboratory of Neuroscience, Department of Biophysics, Wrocław Medical University, Wrocław, Poland

autor

Mozrzymas J. W.

• Laboratory of Neuroscience, Department of Biophysics, Wrocław Medical University, Wrocław, Poland