AMPA and Kainate Receptors

2020 ◽  
Author(s):  
G. Brent Dawe ◽  
Patricia M. G. E. Brown ◽  
Derek Bowie
Keyword(s):  
Ion Channel ◽  
Glutamate Receptor ◽  
Single Channel ◽  
Channel Gating ◽  
Regulatory Proteins ◽  
Kainate Receptors ◽  
Mammalian Brain ◽  
Receptor Field ◽  
Neuronal Excitation ◽  
Ion Channel Proteins

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.

Electrochemical evaluation of chemical selectivity of glutamate receptor ion channel proteins with a multi-channel sensor

1997 ◽  
Vol 12 (5) ◽  
pp. 425-439 ◽  
Author(s):  
Masao Sugawara ◽  
Ayumi Hirano ◽  
Marián Rehák ◽  
Jun Nakanishi ◽  
Kunji Kawai ◽  
...  
Keyword(s):  
Ion Channel ◽  
Glutamate Receptor ◽  
Channel Proteins ◽  
Ion Channel Proteins ◽  
Chemical Selectivity ◽  
Electrochemical Evaluation

Ion channels and disease

2020 ◽  
pp. 246-255
Author(s):  
Frances Ashcroft ◽  
Paolo Tammaro
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Single Channel ◽  
Cell Types ◽  
Channel Structure ◽  
Channel Proteins ◽  
Channel Function ◽  
Ion Channel Proteins ◽  
Single Channel Currents ◽  
Channel Currents

Ion channels are membrane proteins that act as gated pathways for the movement of ions across cell membranes. They are found in both surface and intracellular membranes and play essential roles in the physiology of all cell types. An ever-increasing number of human diseases are now known to be caused by defects in ion channel function. To understand how ion channel defects give rise to disease, it is helpful to understand how the ion channel proteins work. This chapter therefore considers what is known of ion channel structure, explains the properties of the single ion channel, and shows how single-channel currents give rise to action potentials and synaptic potentials.

scholarly journals Adenosine and anoxia reduce N-methyl-D-aspartate receptor open probability in turtle cerebrocortex.

1998 ◽  
Vol 201 (2) ◽  
pp. 289-297 ◽  
Author(s):  
L T Buck ◽  
P E Bickler
Keyword(s):  
Membrane Potential ◽  
Nmda Receptor ◽  
Ion Channel ◽  
Single Channel ◽  
Tissue Injury ◽  
Brain Slices ◽  
Current Amplitude ◽  
Mammalian Brain ◽  
Open Probability ◽  
Experimental Conditions

During normoxia, glutamate and the glutamate family of ion channels play a key role in mediating rapid excitatory synaptic transmission in the central nervous system. However, during hypoxia, intracellular [Ca2+] increases to neurotoxic levels, mediated largely by the N-methyl-D-aspartate (NMDA) subfamily of glutamate receptors. Adenosine has been shown to decrease the magnitude of the hypoxia-induced increase in [Ca2+]i in mammalian brain slices, delaying tissue injury. Turtle brain is remarkably tolerant of anoxia, maintaining a pre-anoxic [Ca2+]i while cerebral adenosine levels increase 12-fold. Employing cell-attached single-channel patch-clamp techniques, we studied the effect of adenosine (200 micromol l-1) and anoxia on NMDA receptor open probability (Popen) and current amplitude. After 60 min of anoxic perfusion, channel Popen decreased by 65 % (from 6.8+/-1.6 to 2.4+/-0.8 %) an effect that could also be achieved with a normoxic perfusion of 200 micromol l-1 adenosine (Popen decreased from 5.8+/-1.1 to 2.3+/-1.2 %). The inclusion of 10 micromol l-1 8-phenyltheophylline, an A1 receptor blocker, prevented the adenosine- and anoxia-induced decrease in Popen. Mean single-channel current amplitude remained at approximately 2.7+/-0.23 pA under all experimental conditions. To determine whether a change in the membrane potential could be part of the mechanism by which Popen decreases, membrane and threshold potential were measured following each experiment. Membrane potential did not change significantly under any condition, ranging from -76.8 to -80.6 mV. Therefore, during anoxia, NMDA receptors cannot be regulated by Mg2+ in a manner dependent on membrane potential. Threshold potentials did decrease significantly following 60 min of anoxic or adenosine perfusion (control -33.3+/-1.9 mV, anoxia -28.4+/-1.5 mV, adenosine -23.4+/-2.8 mV). We conclude that anoxia modulates NMDA receptor activity and that adenosine plays a key role in mediating this change. This is the first direct measurement of ion channel activity in anoxic turtle brain and demonstrates that ion channel regulation is part of the naturally evolved anoxic defence mechanism of this species.

scholarly journals On hysteresis of ion channels

2020 ◽  
Vol 15 ◽  
pp. 26
Author(s):  
Can E. Korman ◽  
Isaak D. Mayergoyz
Keyword(s):  
Ion Channel ◽  
Stochastic Processes ◽  
Action Potentials ◽  
Single Channel ◽  
Hysteresis Loops ◽  
Exit Problem ◽  
Stochastic Nature ◽  
Channel Proteins ◽  
Ion Channel Proteins ◽  
Sodium And Potassium

Ion channel proteins have many conformational (metastable) states and, for this reason, they exhibit hysteresis. This fact is responsible for the non-Markovian stochastic nature of single ion channel recordings. It is suggested in the paper that the stochastic single channel recordings can be modeled as the random outputs of rectangular hysteresis loops driven by stochastic processes. The latter problem can be mathematically treated as an exit problem for stochastic processes or by using the theory of stochastic processes on graphs. It is also demonstrated in the paper that the collective action of sodium and potassium channels responsible for the generation and propagation of action potentials exhibit hysteresis. This demonstration is accomplished by using the inverse problem approach to the nonlinear Hodgkin-Huxley diffusion equation.

Single channel recordings of reconstituted ion channel proteins: an improved technique

1988 ◽  
Vol 411 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Bernhard U. Keller ◽  
Rainer Hedrich ◽  
Winchil L. C. Vaz ◽  
Manuel Criado
Keyword(s):  
Ion Channel ◽  
Single Channel ◽  
Single Channel Recordings ◽  
Channel Proteins ◽  
Ion Channel Proteins ◽  
Improved Technique

scholarly journals Potent neuroprotection after stroke afforded by a double-knot spider-venom peptide that inhibits acid-sensing ion channel 1a

2017 ◽  
Vol 114 (14) ◽  
pp. 3750-3755 ◽  
Author(s):  
Irène R. Chassagnon ◽  
Claudia A. McCarthy ◽  
Yanni K.-Y. Chin ◽  
Sandy S. Pineda ◽  
Angelo Keramidas ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Ion Channel ◽  
Single Channel ◽  
Neuronal Damage ◽  
Neuronal Injury ◽  
Spider Venom ◽  
Mammalian Brain ◽  
Genetic Ablation ◽  
Venom Peptide ◽  
The Brain

Stroke is the second-leading cause of death worldwide, yet there are no drugs available to protect the brain from stroke-induced neuronal injury. Acid-sensing ion channel 1a (ASIC1a) is the primary acid sensor in mammalian brain and a key mediator of acidosis-induced neuronal damage following cerebral ischemia. Genetic ablation and selective pharmacologic inhibition of ASIC1a reduces neuronal death following ischemic stroke in rodents. Here, we demonstrate that Hi1a, a disulfide-rich spider venom peptide, is highly neuroprotective in a focal model of ischemic stroke. Nuclear magnetic resonance structural studies reveal that Hi1a comprises two homologous inhibitor cystine knot domains separated by a short, structurally well-defined linker. In contrast with known ASIC1a inhibitors, Hi1a incompletely inhibits ASIC1a activation in a pH-independent and slowly reversible manner. Whole-cell, macropatch, and single-channel electrophysiological recordings indicate that Hi1a binds to and stabilizes the closed state of the channel, thereby impeding the transition into a conducting state. Intracerebroventricular administration to rats of a single small dose of Hi1a (2 ng/kg) up to 8 h after stroke induction by occlusion of the middle cerebral artery markedly reduced infarct size, and this correlated with improved neurological and motor function, as well as with preservation of neuronal architecture. Thus, Hi1a is a powerful pharmacological tool for probing the role of ASIC1a in acid-mediated neuronal injury and various neurological disorders, and a promising lead for the development of therapeutics to protect the brain from ischemic injury.

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