Kainate Receptors

Author(s):  
Anis Contractor ◽  
Geoffrey T. Swanson
Keyword(s):  
Author(s):  
G. Brent Dawe ◽  
Patricia M. G. E. Brown ◽  
Derek Bowie

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate-type glutamate receptors (AMPARs and KARs) are dynamic ion channel proteins that govern neuronal excitation and signal transduction in the mammalian brain. The four AMPAR and five KAR subunits can heteromerize with other subfamily members to create several combinations of tetrameric channels with unique physiological and pharmacological properties. While both receptor classes are noted for their rapid, millisecond-scale channel gating in response to agonist binding, the intricate structural rearrangements underlying their function have only recently been elucidated. This chapter begins with a review of AMPAR and KAR nomenclature, topology, and rules of assembly. Subsequently, receptor gating properties are outlined for both single-channel and synaptic contexts. The structural biology of AMPAR and KAR proteins is also discussed at length, with particular focus on the ligand-binding domain, where allosteric regulation and alternative splicing work together to dictate gating behavior. Toward the end of the chapter there is an overview of several classes of auxiliary subunits, notably transmembrane AMPAR regulatory proteins and Neto proteins, which enhance native AMPAR and KAR expression and channel gating, respectively. Whether bringing an ion channel novice up to speed with glutamate receptor theory and terminology or providing a refresher for more seasoned biophysicists, there is much to appreciate in this summation of work from the glutamate receptor field.


2010 ◽  
Vol 468 (3) ◽  
pp. 186-189 ◽  
Author(s):  
Ann M. Gregus ◽  
Thomas F. Tropea ◽  
Yanran Wang ◽  
Stefanie C.R. Hauck ◽  
Alberto C.S. Costa ◽  
...  
Keyword(s):  

Neuron ◽  
2003 ◽  
Vol 39 (3) ◽  
pp. 543-553 ◽  
Author(s):  
José Luis Rozas ◽  
Ana V Paternain ◽  
Juan Lerma

2007 ◽  
Vol 27 (9) ◽  
pp. 1540-1552 ◽  
Author(s):  
Selva Baltan Tekkök ◽  
ZuCheng Ye ◽  
Bruce R Ransom

Axonal injury and dysfunction in white matter (WM) are caused by many neurologic diseases including ischemia. We characterized ischemic injury and the role of glutamate-mediated excitotoxicity in a purely myelinated WM tract, the mouse optic nerve (MON). For the first time, excitotoxic WM injury was directly correlated with glutamate release. Oxygen and glucose deprivation (OGD) caused duration-dependent loss of axon function in optic nerves from young adult mice. Protection of axon function required blockade of both α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptors, or removal of extracellular Ca2+. Blockade of N-methyl-D-aspartate receptors did not preserve axon function. Curiously, even extended periods of direct exposure to glutamate or kainate or AMPA failed to induce axon dysfunction. Brief periods of OGD, however, caused glutamate receptor agonist exposure to become toxic, suggesting that ionic disruption enabled excitotoxic injury. Glutamate release, directly measured using quantitative high-performance liquid chromatography, occurred late during a 60-mins period of OGD and was due to reversal of the glutamate transporter. Brief periods of OGD (i.e., 15 mins) did not cause glutamate release and produced minimal injury. These results suggested that toxic glutamate accumulation during OGD followed the initial ionic changes mediating early loss of excitability. The onset of glutamate release was an important threshold event for irreversible ischemic injury. Regional differences appear to exist in the specific glutamate receptors that mediate WM ischemic injury. Therapy for ischemic WM injury must be designed accordingly.


2021 ◽  
pp. 108540
Author(s):  
Jithin D. Nair ◽  
Kevin A. Wilkinson ◽  
Jeremy M. Henley ◽  
Jack R. Mellor

1991 ◽  
Vol 66 (4) ◽  
pp. 1166-1175 ◽  
Author(s):  
D. O. Smith ◽  
C. Franke ◽  
J. L. Rosenheimer ◽  
F. Zufall ◽  
H. Hatt

1. Single-channel properties of desensitizing glutamate-activated channels were analyzed in outside-out patch-clamp recordings from a motoneuron-enriched cell fraction from embryonic chick. A piezo-driven device was used to achieve fast solution exchange at the electrode tip, resulting in maximum activation within 2 ms. 2. Quisqualate/AMPA receptors, with a 13-pS conductance, desensitized rapidly; the desensitization rate depended on agonist concentration but not on membrane potential. When quisqualate was applied slowly, the quisqualate-activated channels desensitized without prior channel opening, indicating desensitization from the closed state. After a 10-ms refractory period, resensitization of all channels required up to 300 ms; resensitization rate did not depend on the duration of the preceding quisqualate application. 3. At agonist concentrations less than or equal to 1 mM, kainate receptors, with a 20-pS conductance, did not desensitize. At kainate concentrations greater than or equal to 1 mM, though, kainate receptors desensitized to a low steady-state conductance within approximately 200 ms. Resensitization of all channels required as long as 3 s, which could render kainate receptors inexcitable during high-frequency activation. 4. Desensitization rates of whole-cell currents were similar to those observed in outside-out mode. Glutamate- and quisqualate-activated responses were similar, suggesting that the rapidly desensitizing quisqualate-sensitive receptor type may dominate the kinetics of whole-cell excitatory postsynaptic currents (EPSCs) in this preparation. 5. It may be concluded that the efficacy of glutamate-mediated synaptic transmission is modulated by differences in the rates of desensitization and resensitization.


2018 ◽  
Vol 44 (3) ◽  
pp. 585-599 ◽  
Author(s):  
Caroline L. Scholefield ◽  
Palmi T. Atlason ◽  
David E. Jane ◽  
Elek Molnár

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