Ligand-Dependent Opening of the Multiple AMPA Receptor Conductance States: A Concerted Model

PLoS One

Ranjita Dutta-Roy¹  Stuart J. Edelstein²  Christian Rosenmund³  Nicolas Le Novère³ 

[1] Department of Medicine Solna, Karolinska Insitutet, 171 76 Stockholm, Sweden;European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK;NWFZ, Charite Universitatsmedizin, 101 17 Berlin, Germany

关键词: Ligand-gated ion channels;    Partial agonists;    Thermodynamics;    Glutamate;    Neurons;    Nicotinic acetylcholine receptors;    Ion channels;    Neurotransmission;   

DOI  :  10.1371/journal.pone.0116616

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Modulation of the properties of AMPA receptors at the post-synaptic membrane is one of the main suggested mechanisms underlying fast synaptic transmission in the central nervous system of vertebrates. Electrophysiological recordings of single channels stimulated with agonists showed that both recombinant and native AMPA receptors visit multiple conductance states in an agonist concentration dependent manner. We propose an allosteric model of the multiple conductance states based on concerted conformational transitions of the four subunits, as an iris diaphragm. Our model predicts that the thermodynamic behaviour of the conductance states upon full and partial agonist stimulations can be described with increased affinity of receptors as they progress to higher conductance states. The model also predicts the existence of AMPA receptors in non-liganded conductive substates. However, the probability of spontaneous openings decreases with increasing conductances. Finally, we predict that the large conductance states are stabilized within the rise phase of a whole-cell EPSC in glutamatergic hippocampal neurons. Our model provides a mechanistic link between ligand concentration and conductance states that can explain thermodynamic and kinetic features of AMPA receptor gating.

【 授权许可】

CC BY