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Protons Potentiate GluN1/GluN3A Currents by Attenuating Their Desensitisation
Kirstie A Cummings1, Gabriela K Popescu1
1Department of Biochemistry, University at Buffalo, SUNY, Buffalo, NY 14214, USA.
Scientific Reports
|March 23, 2016
Summary
Extracellular acidification potentiates glycine-gated currents from N-methyl-D-aspartate (NMDA) GluN1/GluN3A receptors by altering desensitization kinetics. This finding offers a new tool for studying these unique NMDA receptor channels.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- N-methyl-D-aspartate (NMDA) receptors are crucial ion channels in the brain.
- GluN3A subunit expression is developmentally regulated and altered in brain disorders.
- GluN1/GluN3 receptors exhibit unique glycine-gated currents, poorly understood at the cellular level.
Purpose of the Study:
- To investigate the functional modulation of GluN1/GluN3A receptors by extracellular pH.
- To elucidate the mechanisms underlying the unique properties of GluN1/GluN3A receptor currents.
- To identify potential pharmacological tools for studying GluN1/GluN3A receptors in native tissues.
Main Methods:
- Recombinant expression of GluN1/GluN3A receptors.
- Electrophysiological recordings of glycine-gated currents.
- Analysis of current desensitization and recovery kinetics.
- Site-directed mutagenesis to identify key residues.
Main Results:
- Extracellular acidification significantly potentiated glycine-gated currents from GluN1/GluN3A receptors.
- Potentiation was mediated by slower desensitization and faster recovery from desensitization.
- Acidic pH shifts increased equilibrium currents and depolarized the membrane.
- Key residues at the ligand-binding domain interface were identified.
Conclusions:
- Extracellular pH is a potent modulator of GluN1/GluN3A receptor function.
- Acidification alters desensitization kinetics, differentiating GluN1/GluN3A from GluN1/GluN2 receptors.
- This study provides a novel method for detecting and studying GluN1/GluN3A receptor activity.
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