Publication Date:
1995-05-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Traynelis, S F -- Hartley, M -- Heinemann, S F -- NS08549/NS/NINDS NIH HHS/ -- NS28709/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1995 May 12;268(5212):873-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Emory University, Atlanta, GA 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7754371" target="_blank"〉PubMed〈/a〉
Keywords:
*Alternative Splicing
;
Amino Acid Sequence
;
Animals
;
Cell Line
;
Exons
;
Hydrogen-Ion Concentration
;
Lysine/physiology
;
Molecular Sequence Data
;
Mutagenesis, Site-Directed
;
Oocytes
;
Protein Structure, Secondary
;
*Protons
;
Rats
;
Receptors, N-Methyl-D-Aspartate/antagonists &
;
inhibitors/chemistry/genetics/*physiology
;
Spermine/*pharmacology
;
Xenopus
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
