TY - JOUR
T1 - Differential activation of individual subunits in heteromeric kainate receptors
AU - Swanson, Geoffrey T.
AU - Green, Tim
AU - Sakai, Ryuichi
AU - Contractor, Anis
AU - Che, Wesley
AU - Kamiya, Hisao
AU - Heinemann, Stephen F.
N1 - Funding Information:
We thank Gautam Bhave, Mark Farrant, Joel Gallagher, and Robert Gereau for comments on the manuscript and Adam Mitchell for technical assistance. This work was supported by an NRSA fellowship and a NARSAD Young Investigator's Award to G.T.S., a Klingenstein Foundation Fellowship to T.G., an Auen Foundation grant to A.C., grants from the Ministry of Education, Science and Culture, Japan, the Suntory Bioorganic Institute, and the Naito Foundation to R.S., and the NIH (NINDS) and the McKnight Foundation to S.F.H.
PY - 2002/5/16
Y1 - 2002/5/16
N2 - Neuronal kainate receptors are assembled from subunits with dissimilar specificities for agonists and antagonists. The composite biophysical behavior of heteromeric kainate receptors is determined by intersubunit interactions whose nature is unclear. Here we use dysiherbaine, a selective kainate receptor agonist, to show that GluR5 subunits assembled in heteromeric GluR5/KA-2 kainate receptor complexes can gate current without concomitant activation of their partner KA-2 subunits. A long-lasting interaction between dysiherbaine and GluR5 subunits elicits a tonic current from GluR5/KA-2 receptors; subsequent cooperative gating of KA-2 subunits can be elicited by both agonists, such as glutamate, and some classically defined antagonists, such as CNQX. This study demonstrates that each type of subunit within a heteromeric kainate receptor contributes a distinct conductance upon activation by agonist binding, and therefore provides insight into the biophysical function of ionotropic glutamate receptors.
AB - Neuronal kainate receptors are assembled from subunits with dissimilar specificities for agonists and antagonists. The composite biophysical behavior of heteromeric kainate receptors is determined by intersubunit interactions whose nature is unclear. Here we use dysiherbaine, a selective kainate receptor agonist, to show that GluR5 subunits assembled in heteromeric GluR5/KA-2 kainate receptor complexes can gate current without concomitant activation of their partner KA-2 subunits. A long-lasting interaction between dysiherbaine and GluR5 subunits elicits a tonic current from GluR5/KA-2 receptors; subsequent cooperative gating of KA-2 subunits can be elicited by both agonists, such as glutamate, and some classically defined antagonists, such as CNQX. This study demonstrates that each type of subunit within a heteromeric kainate receptor contributes a distinct conductance upon activation by agonist binding, and therefore provides insight into the biophysical function of ionotropic glutamate receptors.
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U2 - 10.1016/S0896-6273(02)00676-1
DO - 10.1016/S0896-6273(02)00676-1
M3 - Article
C2 - 12062042
AN - SCOPUS:0037118264
VL - 34
SP - 589
EP - 598
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -