Single-channel recording of ligand-gated ion channels

2007 ◽  
Vol 2 (11) ◽  
pp. 2826-2841 ◽  
Author(s):  
Martin Mortensen ◽  
Trevor G Smart
Keyword(s):  
Ion Channels ◽  
Single Channel ◽  
Single Channel Recording ◽  
Gated Ion Channels ◽  
Ligand Gated Ion Channels

scholarly journals Mutation of a conserved glutamine residue does not abolish desensitization of acid-sensing ion channel 1

2021 ◽  
Vol 153 (8) ◽  
Author(s):  
Matthew L. Rook ◽  
Megan Miaro ◽  
Tyler Couch ◽  
Dana L. Kneisley ◽  
Maria Musgaard ◽  
...  
Keyword(s):  
Ion Channels ◽  
Single Channel ◽  
Side Chain ◽  
Accelerated Molecular Dynamics ◽  
Acid Sensing Ion Channels ◽  
The Common ◽  
Bond Network ◽  
Dynamics Simulations ◽  
Gated Ion Channels ◽  
Ligand Gated Ion Channels

Desensitization is a common feature of ligand-gated ion channels, although the molecular cause varies widely between channel types. Mutations that greatly reduce or nearly abolish desensitization have been described for many ligand-gated ion channels, including glutamate, GABA, glycine, and nicotinic receptors, but not for acid-sensing ion channels (ASICs) until recently. Mutating Gln276 to a glycine (Q276G) in human ASIC1a was reported to mostly abolish desensitization at both the macroscopic and the single channel levels, potentially providing a valuable tool for subsequent studies. However, we find that in both human and chicken ASIC1, the effect of Q276G is modest. In chicken ASIC1, the equivalent Q277G slightly reduces desensitization when using pH 6.5 as a stimulus but desensitizes, essentially like wild-type, when using more acidic pH values. In addition, steady-state desensitization is intact, albeit right-shifted, and recovery from desensitization is accelerated. Molecular dynamics simulations indicate that the Gln277 side chain participates in a hydrogen bond network that might stabilize the desensitized conformation. Consistent with this, destabilizing this network with the Q277N or Q277L mutations largely mimics the Q277G phenotype. In human ASIC1a, the Q276G mutation also reduces desensitization, but not to the extent reported previously. Interestingly, the kinetic consequences of Q276G depend on the human variant used. In the common G212 variant, Q276G slows desensitization, while in the rare D212 variant desensitization accelerates. Our data reveal that while the Q/G mutation does not abolish or substantially impair desensitization as previously reported, it does point to unexpected differences between chicken and human ASICs and the need for careful scrutiny before using this mutation in future studies.

scholarly journals Mutation of a conserved Gln residue does not abolish desensitization of acid-sensing ion channel 1

2020 ◽  
Author(s):  
Matthew L Rook ◽  
Megan Miaro ◽  
Tyler Couch ◽  
Dana L Kneisley ◽  
Maria Musgaard ◽  
...  
Keyword(s):  
Ion Channels ◽  
Single Channel ◽  
Side Chain ◽  
Accelerated Molecular Dynamics ◽  
Ph Values ◽  
Acid Sensing Ion Channels ◽  
Bond Network ◽  
Dynamics Simulations ◽  
Gated Ion Channels ◽  
Ligand Gated Ion Channels

AbstractDesensitization is a common feature of ligand-gated ion channels although the molecular cause varies widely between channel types. Mutations that substantially reduce or abolish desensitization have been described for many ligand-gated ion channels including glutamate, GABA, glycine and nicotinic receptors but not for acid-sensing ion channels (ASICs) until recently. Mutating Gln276 to a glycine in human ASIC1a was reported to mostly abolish desensitization at both the macroscopic and single channel levels, potentially providing a valuable tool for subsequent studies. However, we find that in both human and chicken ASIC1 the effect of Q276G is modest. In chicken ASIC1, the equivalent Q277G slightly reduces desensitization when using pH 6.5 as a stimulus but desensitizes essentially like wild type when using more acidic pH values. In addition, steady-state desensitization is intact, albeit right-shifted, and recovery from desensitization is accelerated. Molecular dynamics simulations indicate that the Gln277 side chain participates in a hydrogen bond network that might stabilize the desensitized conformation. Consistent with this, destabilizing this network with the Q277N or Q277L mutations largely mimics the Q277G phenotype. In human ASIC1a, Q276G does not substantially reduce desensitization but surprisingly slows entry to and exit from the desensitized state, thus requiring longer agonist applications to reach equilibrium. Our data reveal that while the Q/G mutation does not substantially impair desensitization as previously reported, it does point to unexpected differences between chicken and human ASICs and the need for careful scrutiny before using this mutation in future studies.

Physiology and biophysics of plant ligand-gated ion channels

Plant Biology ◽  
2010 ◽  
Vol 12 ◽  
pp. 80-93 ◽  
Author(s):  
P. Dietrich ◽  
U. Anschütz ◽  
A. Kugler ◽  
D. Becker
Keyword(s):  
Ion Channels ◽  
Gated Ion Channels ◽  
Ligand Gated Ion Channels

scholarly journals Molecular Simulations of Hydrophobic Gating of Pentameric Ligand Gated Ion Channels: Insights into Water and Ions

2021 ◽  
Vol 125 (4) ◽  
pp. 981-994
Author(s):  
Shanlin Rao ◽  
Gianni Klesse ◽  
Charlotte I. Lynch ◽  
Stephen J. Tucker ◽  
Mark S. P. Sansom
Keyword(s):  
Ion Channels ◽  
Molecular Simulations ◽  
Gated Ion Channels ◽  
Ligand Gated Ion Channels

Ligand-gated ion channels as targets of neuroactive insecticides

2021 ◽  
Author(s):  
Makoto Ihara
Keyword(s):  
Ion Channels ◽  
Molecular Mechanisms ◽  
Functional Expression ◽  
X Ray ◽  
Acetylcholine Binding Protein ◽  
Site Selectivity ◽  
Future Drug ◽  
Cl Channels ◽  
Gated Ion Channels ◽  
Ligand Gated Ion Channels

Abstract The Cys-loop superfamily of ligand-gated ion channels (Cys-loop receptors) is one of the most ubiquitous ion channel families in vertebrates and invertebrates. Despite their ubiquity, they are targeted by several classes of pesticides, including neonicotinoids, phenylpyrazols, and macrolides such as ivermectins. The current commercialized compounds have high target site selectivity, which contributes to the safety of insecticide use. Structural analyses have accelerated progress in this field; notably, the X-ray crystal structures of acetylcholine binding protein and glutamate-gated Cl channels revealed the details of the molecular interactions between insecticides and their targets. Recently, the functional expression of the insect nicotinic acetylcholine receptor (nAChR) has been described, and detailed evaluations using the insect nAChR have emerged. This review discusses the basic concepts and the current insights into the molecular mechanisms of neuroactive insecticides targeting the ligand-gated ion channels, particularly Cys-loop receptors, and presents insights into target-based selectivity, resistance, and future drug design.

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