The NR3B subunit does not alter the anesthetic sensitivities of recombinant N-methyl-D-aspartate receptors.
The N-methyl-D-aspartate (NMDA) receptor NR3B subunit co-assembles with NR1 and NR2 subunits to form a receptor complex with distinct channel properties. In the present study, we investigated the effects of co-expression of the NR3B subunit on the anesthetic sensitivities of NMDA receptors for NR1/NR2 channels expressed in Xenopus oocytes. Although the NR3B subunit prominently reduced the current amplitude of NR1/NR2A-B channels, the sensitivities of NR1/NR2A-B channels to Mg2+, ketamine, isoflurane, nitrous oxide, and ethanol were not altered by coexpression of the NR3B subunit. These results suggest that the anesthetic sensitivities of NMDA receptors do not depend on the presence or absence of the NR3 subunit. Mutations of two amino acid residues in the NR3B subunit at positions homologous to the N and N + 1 sites in the NR1 and NR2 subunits, which constitute the blocking sites for Mg2+ and ketamine, did not affect the sensitivities of NR1/NR2B/NR3B channels to Mg2+, ketamine and isoflurane. Thus, the amino acid residues at the N and N + 1 sites in NR3 subunits are unlikely to be involved in the formation of channel blocking sites in NR1/NR2/NR3 channels.
Yamakura
Tomohiro
T
*Division of Anesthesiology, Niigata University Graduate School of Medical and †Dental Sciences; Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
Askalany
Ahmed R
AR
Petrenko
Andrey B
AB
Kohno
Tatsuro
T
Baba
Hiroshi
H
Sakimura
Kenji
K
D000595:Amino Acid Sequence; D000777:Anesthetics / Q000494:pharmacology*; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009609:Nitrous Oxide / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D014981:Xenopus
D000777:Anesthetics; D000778:Anesthetics, Dissociative; D018685:Anesthetics, Inhalation; D002492:Central Nervous System Depressants; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; C501155:NR3B NMDA receptor; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D000431:Ethanol; D018698:Glutamic Acid; D007649:Ketamine; D009609:Nitrous Oxide; D005998:Glycine