Non-N-mrthyl-D-aspartate glutamate receptors are responsible for fast
excitatory neurotransmission in the mammalian CNS. These receptors are
rapidly activated and desensitized in the presence of glutamate, and
are often further subdivided into alpha-amino-3-hydroxy-5-methyl-4-iso
xazole proprionic acid and kainate receptors based on their selective
agonists. Non-NMDA glutamate receptors are composed of multiple subuni
ts which recently have been cloned, and studies on the recombinant glu
tamate receptors have helped clarify the distinctions between AMPA and
kainate-preferring glutamate receptors. Although the subunits which m
ake up both AMPA and kainate receptors have a widespread distribution,
most currents recorded in vivo are characteristic of recombinant AMPA
receptors. To help clarify the functional role of high-affinity kaina
te receptors, we have characterized the expression of a high-affinity
kainate receptor subunit, KA2, in cultured hippocampal neurons. Using
immunocytochemistry, we found that KA2 was expressed in hippocampal ne
urons at all times during the development of the cells in culture, and
the subunit was enriched in dendritic spines after about 14 days. The
subcellular distribution of KA2 paralleled that of the AMPA receptor
subunit GluR1, with the AMPA and kainate subunits being colocalized at
all times in culture. The enriched KA2 immunoreactivity co-localized
with the synaptic vesicle protein synaptophysin at the resolution of l
ight microscopy, indicating synaptic localization of KA2. Although the
kainate subunit KA2 co-localized with the AMPA subunit GluR1, co-immu
noprecipitation experiments demonstrated a direct interaction between
the AMPA receptor subunits GluR1 and GluR2/3, but not between GluR1 an
d the kainate subunits GluR6/7 or KA2. We therefore, conclude that bot
h AMPA and kainate receptor subunits are enriched in the same dendriti
c spines, yet do not combine to form receptor complexes.