Title

Liposome reconstitution and modulation of recombinant N-methyl-D-aspartate receptor channels by membrane stretch

RIS ID

105698

Publication Details

Kloda, A., Lua, L., Hall, R., Adams, D. J. & Martinac, B. (2007). Liposome reconstitution and modulation of recombinant N-methyl-D-aspartate receptor channels by membrane stretch. Proceedings of the National Academy of Sciences of USA, 104 (5), 1540-1545.

Abstract

In this study, the heteromeric N-methyl-D-aspartate (NMDA) receptor channels composed of NR1a and NR2A subunits were expressed, purified, reconstituted into liposomes, and characterized by using the patch clamp technique. The protein exhibited the expected electrophysiological profile of activation by glutamate and glycine and internal Mg2+ blockade. We demonstrated that the mechanical energy transmitted to membrane-bound NMDA receptor channels can be exerted directly by tension developed in the lipid bilayer. Membrane stretch and application of arachidonic acid potentiated currents through NMDA receptor channels in the presence of intracellular Mg 2+. The correlation of membrane tension induced by either mechanical or chemical stimuli with the physiological Mg2+ block of the channel suggests that the synaptic transmission can be altered if NMDA receptor complexes experience local changes in bilayer thickness caused by dynamic targeting to lipid microdomains, electrocompression, or chemical modification of the cell membranes. The ability to study gating properties of NMDA receptor channels in artificial bilayers should prove useful in further study of structure-function relationships and facilitate discoveries of new therapeutic agents for treatment of glutamate-mediated excitotoxicity or analgesic therapies.

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Link to publisher version (DOI)

http://dx.doi.org/10.1073/pnas.0609649104