Auxiliary proteins promote modal gating of AMPA- and kainate-type glutamate receptors.
The gating behavior of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors is modulated by association with the auxiliary proteins: transmembrane AMPA receptor regulatory proteins (TARPs) and neuropilin tolloid-like (Netos), respectively. Although the mechanisms underlying receptor modulation differ for both AMPA and kainate receptors, association with these auxiliary subunits results in the appearance of a slow component in the decay of ensemble responses to rapid applications of saturating concentrations of glutamate. We show here that these components arise from distinct gating behaviors, characterized by substantially higher open probability (Popen ), which we only observe when core subunits are associated with their respective auxiliary partners. We refer to these behaviors as gating modes, because individual receptors switch between the low- and high-Popen gating on a time-scale of seconds. At any given time, association of AMPA and kainate receptors with their auxiliary subunits results in a heterogeneous receptor population, some of which are in the high-Popen mode and others that display gating behavior similar to that seen for receptors formed from core subunits alone. While the switching between modes is infrequent, the presence of receptors displaying both types of gating has a large impact on both the kinetics and amplitude of ensemble currents similar to those seen at synapses.
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8066, USA; Institute of Chinese Integrative Medicine, Hebei Medical University, Hebei, China.
Wei
W
Zhang
Suma Priya Sudarsana
SP
Devi
Susumu
S
Tomita
James R
JR
Howe
D000200:Action Potentials; D002460:Cell Line; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D007608:Kainic Acid / Q000378:metabolism; D055503:Protein Multimerization; D021122:Protein Subunits / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism*
D018698:Glutamic Acid; D007608:Kainic Acid; D021122:Protein Subunits; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors
Neto2; TARPs; glutamate; kinetics; modulation