Role of the Ion Channel Extracellular Collar in AMPA Receptor Gating.

ABSTRACT: AMPA subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission and are implicated in numerous neurological diseases. Ionic currents through AMPA receptor channels can be allosterically regulated via different sites on the receptor protein. We used site-directed mutagenesis and patch-clamp recordings to probe the ion channel extracellular collar, the binding region for noncompetitive allosteric inhibitors. We found position and substitution-dependent effects for introduced mutations at this region on AMPA receptor gating. The results of mutagenesis suggested that the transmembrane domains M1, M3 and M4, which contribute to the ion channel extracellular collar, undergo significant relative displacement during gating. We used molecular dynamics simulations to predict an

SUBMITTER: Yelshanskaya MV 

PROVIDER: S-EPMC5430913 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature