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Science 12 May 1995:
Vol. 268. no. 5212, pp. 873 - 876
DOI: 10.1126/science.7754371
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Articles

Science, Vol 268, Issue 5212, 873-876
Copyright © 1995 by American Association for the Advancement of Science

articles

Control of proton sensitivity of the NMDA receptor by RNA splicing and polyamines

SF Traynelis, M Hartley, and SF Heinemann

Department of Pharmacology, Emory University, Atlanta, GA 30322, USA.

The function of the N-methyl-D-aspartate (NMDA)-preferring glutamate receptor can be regulated by extracellular pH, a process that may be important during ischemia in the brain or during seizures. Protons inhibit NMDA receptor function by 50 percent at pH 7.3 through interactions with the NR1 subunit, and both polyamines and NR1 exon 5 potentiate receptor function through relief of the tonic proton inhibition present at physiological pH. A single amino acid (lysine 211) was identified that mediates the effects of exon 5 in the rat brain. Electroneutral substitutions at this position restored pH sensitivity and, consequently, polyamine relief of tonic inhibition. This effect, together with the structural similarities between polyamines and the surface loop encoded by exon 5, suggest that exon 5 may act as a tethered pH-sensitive constitutive modulator of NMDA receptor function.


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