J Neurophysiol (February 1, 2003). 10.1152/jn.00629.2002
Submitted on Submitted 2 August 2002; accepted in final form 14 October 2002
Excitatory Amino Acid Receptors of the Electrosensory System:
The NR1/NR2B N-Methyl-D-Aspartate Receptor
Erik
Harvey-Girard and
Robert J.
Dunn
Research Institute of the McGill University Health Center,
Montreal, Quebec H3G1A4, Canada
Harvey-Girard, Erik and
Robert J. Dunn.
Excitatory Amino Acid Receptors of the Electrosensory System:
The NR1/NR2B N-Methyl-D-Aspartate Receptor. J. Neurophysiol. 89: 822-832, 2003. The amino acid sequence of the
N-methyl-D-aspartate (NMDA) receptor
subunit NR2B from the brown ghost knife fish Apteronotus leptorhynchus has been determined and compared with the sequence of the murine NR2B. This comparison revealed high levels of sequence conservation throughout the ligand binding and membrane spanning segments. The functional properties of the NR1 and NR2B receptor complex were examined by coexpression in HEK cells. The recombinant AptNR1/NR2B receptors produced robust currents after stimulation with
glutamate or NMDA in the presence of glycine. Measurements of the
concentration dependencies for these agonists indicated that the
agonist binding sites on the apteronotid receptor are highly conserved,
with nearly identical agonist affinities to those of the murine
NR1/NR2B receptor. The kinetic responses of the fish receptor were also
highly conserved, with deactivation rates for the AptNR2B receptor
matching those of the murine NR2B containing receptor. Evidently, most
of the unique functional properties that reside in the NR2B receptor
subunit have been well conserved in teleost NMDA receptors. On the
other hand, the apteronitid receptor displayed a lowered sensitivity to
voltage-dependent Mg2+ block and a reduced
affinity for the NR2B-specific noncompetitive antagonist ifenprodil. We
conclude that the functional properties that result from the
incorporation of the NR2B receptor in the NMDA receptor complex have
been maintained since the evolutionary divergence of teleost and
mammalian organisms.
