RT Journal Article
SR Electronic
T1 Control of Voltage-Independent Zinc Inhibition of NMDA Receptors by the NR1 Subunit
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6163
OP 6175
DO 10.1523/JNEUROSCI.18-16-06163.1998
VO 18
IS 16
A1 Stephen F. Traynelis
A1 Michele F. Burgess
A1 Fang Zheng
A1 Polina Lyuboslavsky
A1 Jennifer L. Powers
YR 1998
UL http://www.jneurosci.org/content/18/16/6163.abstract
AB Zinc inhibits NMDA receptor function through both voltage-dependent and voltage-independent mechanisms. In this report we have investigated the role that the NR1 subunit plays in voltage-independent Zn2+ inhibition. Our data show that inclusion of exon 5 into the NR1 subunit increases the IC50 for voltage-independent Zn2+inhibition from 3-fold to 10-fold when full length exon 22 is also spliced into the mature NR1 transcript and the NMDA receptor complex contains the NR2A or NR2B subunits; exon 5 has little effect on Zn2+ inhibition of receptors that contain NR2C and NR2D. Mutagenesis within exon 5 indicates that the same residues that control proton inhibition, including Lys211, also control the effects of exon 5 on Zn2+inhibition. Amino acid exchanges within the NR1 subunit but outside exon 5 (E181Q, E339Q, E342Q, N616R, N616Q, D669N, D669E, C744A, and C798A) that are known to decrease the pH sensitivity also decrease the Zn2+ sensitivity, and concentrations of spermine that relieve tonic proton inhibition also relieve Zn2+ inhibition. In summary, our results define the subunit composition of Zn2+-sensitive NMDA receptors and provide evidence for structural convergence of three allosteric regulators of receptor function: protons, polyamines, and Zn2+.