Ligand gated ion channel mutants ion channel gating. Medical search. Frequent questions

Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors. (ibpc.fr)
2013. Structural basis for ion permeation mechanism in pentameric ligand-gated ion channels . (ibpc.fr)

Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels of the central and peripheral nervous system that regulate synaptic activity from both pre- and postsynaptic sites. (aspetjournals.org)
The manner in which ethanol interacts with mutant receptors will provide information on the molecular nature of the site at which these compounds interact with these receptors. (grantome.com)
The strong expression of ATP-gated P2X3 receptors by a subpopulation of sensory neurons indicates the important role of these membrane proteins in nociceptive signaling in health and disease, especially when the latter is accompanied by chronic pain syndromes. (gozmusic.org)
2010). Lipid raft association and cholesterol sensitivity of P2X1-4 receptors for ATP: chimeras and point mutants identify intracellular amino-terminal residues involved in lipid regulation of P2X1 receptors. (gozmusic.org)
Among ligand-gated channel genes, the genes encoding gamma-aminobutyric acid (GABA) receptors are considered a hotspot for susceptibility of IGE because of the extensive distribution of GABA receptors in the central nervous system (CNS), their potential for postsynaptic inhibition, and regulation by therapeutically important antiepileptic drugs [ 10 ]. (hindawi.com)
Malfunction of the gene encoding these subunits influences the expression, gating of the ion channels, and trafficking of GABA receptors to the cellular surface [ 13 ]. (hindawi.com)

the overall structure of this ion channel is found to share some common features with voltage-gated ion channels, although several unique, TRP-specific features are also characterized. (nature.com)
Marine toxins have potent actions on diverse sodium ion channels regulated by transmembrane voltage (voltage-gated ion channels) or by neurotransmitters (nicotinic acetylcholine receptor channels). (mdpi.com)

This influx of calcium ions in turn controls the beating of the tail and, thereby, steers the sperm cell towards the egg. (elifesciences.org)
In zebrafish sperm, a more alkaline pH inside the cell causes calcium ions to flow in and this influx of calcium ions triggers a unique spinning-like swimming movement that is different from the swimming of other sperm from other species. (elifesciences.org)
When the presynaptic neuron is stimulated, calcium channels open and the influx of calcium ions into the axon terminal triggers a cascade of events leading to the release of neurotransmitter. (org.es)

His interests and those of his research groups have included exploring the mechanisms of ion permeation and selectivity in ion channels, the relationship between the molecular structure and the physiological function of channels, such as those of the inhibitory neurotransmitter receptor glycine channel and the olfactory cyclic nucleotide-gated channel, and investigating the factors that determine their ion permeation, selectivity and conductance. (edu.au)
His current research is now concentrating on liquid junction potential effects on membrane potential measurements and their role in ion permeation and selectivity, and the reliability of their calculation and measurement, including the importance of using ion activities in their calculation in many situations, and complications that can arise in solutions containing polyvalent ion mixtures. (edu.au)

2015. Allosteric and hyperekplexic mutant phenotypes investigated on an α1 glycine receptor transmembrane structure . (ibpc.fr)
Voltage-gated and ligand-gated are key ion channel genes that have been linked to distinct epilepsy phenotypes [ 9 ]. (hindawi.com)
Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment. (bvsalud.org)

Finally, in Chapter 4, we discuss the use of hydroxy acids to scan the α-M1 transmembrane helix of the nAChR for residues that undergo structural rearrangements during gating. (caltech.edu)
Chimeric receptor subunits and site-directed mutants were used to localize sequence determinants of cocaine affinity to: 1) a region of α4 located between residues 128 and 267 and 2) a site within the pore-lining M2 domain of β4 that includes the 13′ phenylalanine residue. (aspetjournals.org)
Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K + ion occupancy, and K + conductance. (nature.com)
2011). Cysteine scanning mutagenesis (residues Glu52-Gly96) of the human P2X1 receptor for ATP: mapping agonist binding and channel gating. (gozmusic.org)
The channel is formed by an inner group of five helices and putatively gated by bulky hydrophobic residues. (tcdb.org)

Gamma-aminobutyric acid (GABA) receptor is a ligand-gated chloride channel. (hindawi.com)

An apparent Mg 2+ ion was bound between monomers at a conserved site in the cytoplasmic domain suggesting a mechanism to link gating of the pore to the intracellular concentration of Mg 2+ . (tcdb.org)

Inwardly rectifying potassium (Kir) channels open at the 'helix bundle crossing' (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. (nature.com)
Kir channels consist of only two transmembrane helices plus an extensive C-terminal cytoplasmic tail of the channel pore. (nature.com)
Recent investigations have suggested distinct molecular determinants responsible for agonist binding and channel opening for transmembrane flux of sodium, calcium and potassium ions. (gozmusic.org)
2015). Geometric rules of channel gating inferred from computational models of the P2X receptor transmembrane domain. (gozmusic.org)
This review examines the historical perspective of the study of conotoxin peptides active on sodium channels gated by transmembrane voltage, which has led to recent advances in ion channel research made possible with the exploitation of the diversity of these marine toxins. (mdpi.com)

The δ subunit mRNA was present at wild-type levels in the mutant granule cells, indicating a post-translational loss of the δ subunit. (jneurosci.org)
Conversely, the 13′ residue of the β4 subunit M2 region is important in determining acetylcholine potency, indicating a role for this residue in agonist binding/gating processes. (aspetjournals.org)
The unusual sensitivity of αβδ receptor channels to neurosteroid modulation prompted investigation of whether this high sensitivity was dependent on the δ subunit or the low-efficacy channel function that it confers. (jneurosci.org)

Although the physiological relevance of endogenous partial agonists remains poorly understood, the possibility of reversible augmentation of partial agonist efficacy by endogenous modulators raises the interesting possibility of plasticity at the level of agonist-dependent gating. (jneurosci.org)

2011). The Intracellular Amino Terminus Plays a Dominant Role in Desensitization of ATP-gated P2X Receptor Ion Channels. (gozmusic.org)

Bestrophin (BEST1-4) ligand-gated chloride (Cl - ) channels are activated by calcium (Ca 2+ ). (elifesciences.org)
This channel is activated by signalling molecules inside cells, called 'cyclic nucleotides', and its activity ultimately leads to calcium ions flowing into the sperm cell's tail. (elifesciences.org)

Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. (nature.com)
The present data reveal how individual protonation events change the electrostatic microenvironment of the pore, resulting in step-wise alterations of ion pooling, and hence conductance, that appear as 'gated' substates. (nature.com)
In the G178D structure, the HBC gate is slightly wider than in previous structures, and molecular dynamics (MD) simulations demonstrate rapid wetting of the G178D pore at the HBC region, followed by further expansion and K + conductance through the channel. (nature.com)
Unlike other channels, opening of the pore is due to the repositioning of tethered pore-lining helices within a surrounding protein shell that dramatically widens a neck of the pore through a concertina of amino acid rearrangements. (elifesciences.org)
The channel comprises five BEST1 subunits arranged symmetrically around a central ion pore that is ~95 Å long. (elifesciences.org)
2008 ). A periplasmic gate is centered about a proline-induced kink of the pore-lining helix. (tcdb.org)
The narrowest constriction along the pore is a hydrophobic gate, likely forming an energetic barrier to ion flux. (tcdb.org)

Potassium channels are present in all types of cells and play critical roles in control of multiple physiological processes. (nature.com)
In 2009, researchers identified a potassium ion channel, called CNGK, that starts the electrical signal in the sperm cells of sea urchins. (elifesciences.org)

From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a significant aspect for the diagnosis and treatment of heart diseases. (bvsalud.org)
Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. (bvsalud.org)
Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. (bvsalud.org)

In sea urchin sperm, a cyclic nucleotide-gated K + channel (CNGK) mediates a cGMP-induced hyperpolarization that evokes Ca 2+ influx. (elifesciences.org)

Partly because bestrophin channels have no sequence or structural similarity to other ion channels, the molecular mechanisms underlying gating are unknown. (elifesciences.org)

Ion channel gating and conductance are classically understood as separate processes. (nature.com)

We reported the crystal structure of a chicken Kir2.2[G178D] mutant channel 12 , in which the introduced G178D mutations at the HBC functionally stabilize the open conformation, a strategy used previously to obtain an open crystal structure of a bacterial homolog KirBac3.1 13 . (nature.com)
Perplexingly, however, even though the Ca 2+ clasps were occupied by Ca 2+ ions in the X-ray structure, the conformation of the neck was too narrow to allow hydrated ions to pass. (elifesciences.org)

Analysis of the effects of incorporation of mutant and chimeric subunits also permitted identification of sequence elements important in receptor activation. (aspetjournals.org)
The neck serves as both the activation and the inactivation gate. (elifesciences.org)
These experiments made it clear that the neck forms the activation gate that opens in response to the binding of cytosolic Ca 2+ ions. (elifesciences.org)
A picture is emerging of sperm channel orthologues that employ different activation mechanisms and serve different functions. (elifesciences.org)

These findings suggest that while channel proteins found in sperm cells from different species look similar and serve similar roles, they are activated in ways that can be very different. (elifesciences.org)
In this respect, and also with respect to topology, MIT family members resemble channel proteins. (tcdb.org)

Mutations in ion channel genes have been identified as a common cause of IGE. (hindawi.com)

This implicates expansion of the HBC as a critical step in Kir channel opening, as seen in a recent Kir6.2 structure 11 . (nature.com)
Studies of these toxins have focused on varied aspects of venom peptides ranging from evolutionary relationships of predator and prey, biological actions on excitable tissues, potential application as pharmacological intervention in disease therapy, and as part of multiple experimental approaches towards an understanding of the atomistic characterization of ion channel structure. (mdpi.com)

Here, we present a series of cryo-electron microscopy structures of chicken BEST1, determined at 3.1 Å resolution or better, that represent the channel's principal gating states. (elifesciences.org)

SPIDR was tested using the potent and selective 16-amino acid peptide α -conotoxin MII ligand and the α 3 β 2 -nicotinic acetylcholine receptor (nAChR) isoform. (biomedcentral.com)

The nAChR is a ligand-gated ion channel (LGIC) and the M₂AChR is a G-protein-coupled receptor (GPCR). (caltech.edu)
SPIDR incorporates a genetic algorithm-based, heuristic search procedure, which was used to explore the ligand binding domain of the α 3 β 2 -nAChR isoform using a library consisting of 640,000 α -conotoxin MII peptide analogs. (biomedcentral.com)

Hydroxy acids disrupt hydrogen bonding in protein backbones and thus provide a means to detect backbone interactions that form or break during gating. (caltech.edu)

Small-molecule Peptide-Influenced Drug Repurposing (SPIDR) was developed to identify small molecule drugs that target a specific receptor by exploring the conformational binding space of peptide ligands. (biomedcentral.com)
2012). A Dual Polybasic Motif Determines Phosphoinositide Binding and Regulation in the P2X Channel Family. (gozmusic.org)

It was previously thought that this CNGK channel is found only in animals without a backbone (i.e. in invertebrates). (elifesciences.org)

As a proof of principle, we validated our approach by mixed-culture experiments of an Escherichia coli wild type with two metabolic mutants. (gozmusic.org)

In the present study, we carry out detailed single-channel analyses of cKir2.2[G178D] and hKir2.1[G177E] channels that reveal striking sub-state gating behavior. (nature.com)

Previous studies of a D89N mutant led to the proposal that a negative charge at D89 was essential for receptor function. (caltech.edu)
Taken together, these results suggest a correlation between the putative iGluR-like channel function and the alteration of root growth and development in the Arabidopsis roots. (intechopen.com)

Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. (nature.com)

The actions of ethanol on the central nervous system involve a number of biochemical sites, including the ligand-gated ion channels. (grantome.com)
La acetilcolina ejerce un rol preponderante como neuromodulador en el sistema nervioso central, principalmente a nivel de los circuitos neuronales asociados a cognición, memoria, aprendizaje, atención, recompensa y procesamiento de la información sensorial, modificando su respuesta frente a estímulos internos y externos. (uns.edu.ar)
Una de las subunidades de receptor nicotínico más abundantes en el sistema nervioso central es α7, tradicionalmente reconocida por su capacidad para formar receptores homoméricos de origen evolutivo más ancestral. (uns.edu.ar)
En el presente trabajo de tesis se descifraron las bases moleculares de la activación y modulación de los receptores nicotínicos α7 homoméricos y heteroméricos, utilizando principalmente técnicas electrofisiológicas, con el fin de comprender el impacto diferencial de ambos subtipos en la señalización colinérgica del sistema nervioso central. (uns.edu.ar)

Continuous growth on antagonist also leads to impairment of root meristem size, which suggests that iGluR-like channels may play a role in meristem maintenance. (intechopen.com)

To uncover the role of iGluR-like channels in plant root growth, we used a comprehensive set of compounds known to alter iGluR channels in the neurons. (intechopen.com)

Anatomy21

Organisms16

Diseases2

Chemicals and Drugs146

Analytical, Diagnostic and Therapeutic Techniques and Equipment18

Phenomena and Processes48

Disciplines and Occupations4

Technology, Industry, Agriculture1

Information Science3

Health Care1

Pentameric2

Receptors6

Voltage-gated ion channels2

Influx of calcium ions3

Permeation2

Phenotypes3

Residues5

Chloride channel1

Mechanism1

Transmembrane5

Subunit3

Agonist1

Intracellular1

Calcium2

Pore7

Potassium2

Sodium3

Cyclic1

Structural1

Conductance1

Conformation2

Activation4

Proteins2

Mutations1

Structure2

Structures1

Amino1

NAChR2

Interactions1

Binding2

Backbone1

Wild-type1

Present1

Function2

Recordings1

Central4

Suggests1

Role1