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Revealing Dynamically-Organized Receptor Ion Channel Clusters in Live Cells by a Correlated Electric Recording and Super-Resolution Single-Molecule Imaging

Abstract

N-methyl-D-aspartate (NMDA) receptor ion-channel is activated by the binding of ligands, along with the application of action potential, important for synaptic transmission and memory functions. Despite substantial knowledge of structure and function, the gating mechanism of NMDA receptor ion channel for electric on-off signals is still a topic of debate. We investigate the NMDA receptor partition distribution and the associated channel’s open-close electric signal trajectories using a combined approach of correlating single-molecule fluorescence photo-bleaching, single-molecule super-resolution imaging, and single-channel electric patch-clamp recording. Identifying the compositions of NMDA receptor, their spatial organization and distributions over live cell membrane, we observe that NMDA receptors are organized inhomogeneously: nearly a half of the receptor proteins are individually dispersed; whereas, others exist in heterogeneous clusters of around 50 nm in size as well as co-localized within diffraction limited imaging area. We attribute that inhomogeneous interactions and partitions of the NMDA receptors can be a cause for heterogeneous gating mechanism of NMDA receptor in living cells. Furthermore, comparing the imaging results with the ion-channel electric current recording, we propose that the clustered NMDA receptors may be responsible for the variation in the current amplitude observed in the on-off two-state ion-channel electric signal trajectories. Our findings shed a new light on the fundamental structure-function mechanism of NMDA receptor and presents a conceptual advancement of ion-channel mechanism in living cells.

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Publication details

The article was received on 29 Nov 2017, accepted on 19 Jan 2018 and first published on 02 Feb 2018


Article type: Paper
DOI: 10.1039/C7CP08030A
Citation: Phys. Chem. Chem. Phys., 2018, Accepted Manuscript
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    Revealing Dynamically-Organized Receptor Ion Channel Clusters in Live Cells by a Correlated Electric Recording and Super-Resolution Single-Molecule Imaging

    R. Yadav and H. P. Lu, Phys. Chem. Chem. Phys., 2018, Accepted Manuscript , DOI: 10.1039/C7CP08030A

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