Abstract
A cDNA encoding a full-length N-methyl-D-aspartate (NMDA) receptor subunit 1, hNR1, was isolated from a human brain cDNA library. The hNR1 cDNA encodes an open reading frame of approximately 2.7 kb that shares high homology with the rat brain NMDA receptor subunit 1 and the mouse zeta 1 subunit. The hNR1 sequence, however, diverges from the rodent and murine homologs near the C terminus, suggesting that they represent alternatively spliced messages of the same gene. Oocytes injected with cRNA synthesized from the hNR1 cDNA express glutamate and NMDA-activated currents in the presence of glycine. Currents are blocked by the NMDA-receptor-specific antagonists 2-amino-5-phosphovaleric acid and 7-chlorokynurenate, and the open channel blockers MK-801 and phencyclidine, by Mg2+ ions in a voltage-dependent manner, and by Zn2+. Expressed hNR1 homomeric receptor channels exhibit the high Ca2+ permeability characteristic of neuronal NMDA receptors. Therefore, the cDNA clone hNR1 codes for a human brain NMDA receptor subunit cognate to the rodent and murine brain NR1 subunits.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Amino Acid Sequence
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Animals
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Cloning, Molecular
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DNA / genetics
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DNA / isolation & purification
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Dizocilpine Maleate / pharmacology
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Female
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Frontal Lobe / metabolism*
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Gene Library
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Glutamates / pharmacology
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Glutamic Acid
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Glycine / pharmacology
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Humans
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Ibotenic Acid / analogs & derivatives
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Ibotenic Acid / pharmacology
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Kainic Acid / pharmacology
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Macromolecular Substances
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Molecular Sequence Data
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N-Methylaspartate / pharmacology
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Oocytes / drug effects
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Oocytes / physiology
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Quisqualic Acid / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / genetics*
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Receptors, N-Methyl-D-Aspartate / physiology*
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Sequence Homology, Amino Acid
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Transcription, Genetic
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Xenopus laevis
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Substances
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Glutamates
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Macromolecular Substances
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RNA, Messenger
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Receptors, N-Methyl-D-Aspartate
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Ibotenic Acid
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Glutamic Acid
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N-Methylaspartate
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Dizocilpine Maleate
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2-Amino-5-phosphonovalerate
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Quisqualic Acid
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DNA
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Kainic Acid
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Glycine