Ethanol and the GABAA Receptor-Gated Chloride Ion Channel

1991 ◽  
pp. 49-76 ◽  
Author(s):  
A. Leslie Morrow ◽  
Pascale Montpied ◽  
Steven M. Paul
Keyword(s):  
Ion Channel ◽  
Gabaa Receptor ◽  
Chloride Ion

scholarly journals P149 The intracellular chloride channel 4 (CLIC4) plays an important role in systemic sclerosis fibroblast activation

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Christopher Wasson ◽  
Rebecca Ross ◽  
Ruth Morton ◽  
Jamel Mankouri ◽  
Francesco Del Galdo
Keyword(s):  
Systemic Sclerosis ◽  
Ion Channel ◽  
Smooth Muscle Actin ◽  
Chloride Ion ◽  
Dermal Fibroblasts ◽  
Cancer Associated Fibroblasts ◽  
Alpha Smooth Muscle Actin ◽  
Direct Role ◽  
Fibroblast Activation ◽  
Intracellular Chloride

Abstract Background/Aims  The intracellular chloride ion channel CLIC4 mediates the activation of cancer associated fibroblasts. Interestingly, systemic sclerosis (SSc) fibroblasts display a number of similar properties to cancer associated fibroblasts. Tissue fibrosis in SSc is driven by active fibroblasts (myofibroblasts). Therefore in this study we investigated the role of CLIC4 in SSc fibroblast activation. Methods  Dermal fibroblasts were obtained from full thickness skin biopsies from SSc patients (early-diffuse). RNA and protein were collected from the fibroblasts and CLIC4 transcript and protein levels were assessed by qPCR and western blot. SSc patient fibroblasts were treated with the chloride ion channel inhibitors NPPB and IAA-94. Results  CLIC4 was found to be expressed at significantly higher levels in SSc patients fibroblasts compared to healthy controls, at both the transcript (3.7 fold) and protein (1.7 fold) levels. Inhibition of the TGF-β signalling pathway led to reduced CLIC4 expression in SSc fibroblasts, confirming this pathway as the main driver of CLIC4 expression. Finally, treatment of SSc fibroblasts with small molecule inhibitors that target the channel led to reduced expression of the myofibroblast markers collagen type 1 and alpha-smooth muscle actin, suggesting a direct role for CLIC4 in SSc associated skin fibrosis. Conclusion  We have identified a novel role for CLIC4 in SSc myofibroblast activation, which further strengthen the similarities between SSc fibroblasts and cancer associated fibroblasts. Furthermore this study highlights this channel as a novel target for therapeutic intervention. Disclosure  C. Wasson: None. R. Ross: None. R. Morton: None. J. Mankouri: None. F. Del Galdo: None.

Fluorescence-Based High Throughput Screening Technologies for Natural Chloride Ion Channel Blockers

2018 ◽  
Vol 31 (12) ◽  
pp. 1332-1338 ◽  
Author(s):  
Rong Xu ◽  
Yuan Xiao ◽  
Yan Liu ◽  
Bo Wang ◽  
Xing Li ◽  
...  
Keyword(s):  
Ion Channel ◽  
High Throughput ◽  
High Throughput Screening ◽  
Chloride Ion ◽  
Channel Blockers ◽  
Ion Channel Blockers

scholarly journals Quantized Three-Ion-Channel Neuron Model for Neural Action Potentials

Quantum ◽  
2020 ◽  
Vol 4 ◽  
pp. 224 ◽  
Author(s):  
Tasio Gonzalez-Raya ◽  
Enrique Solano ◽  
Mikel Sanz
Keyword(s):  
Ion Channel ◽  
Quantum State ◽  
Channel Model ◽  
Single Channel ◽  
Chloride Ion ◽  
Electric Response ◽  
Nervous Impulse ◽  
Electric Circuits ◽  
Quantum Regime ◽  
Voltage Spike

The Hodgkin-Huxley model describes the conduction of the nervous impulse through the axon, whose membrane's electric response can be described employing multiple connected electric circuits containing capacitors, voltage sources, and conductances. These conductances depend on previous depolarizing membrane voltages, which can be identified with a memory resistive element called memristor. Inspired by the recent quantization of the memristor, a simplified Hodgkin-Huxley model including a single ion channel has been studied in the quantum regime. Here, we study the quantization of the complete Hodgkin-Huxley model, accounting for all three ion channels, and introduce a quantum source, together with an output waveguide as the connection to a subsequent neuron. Our system consists of two memristors and one resistor, describing potassium, sodium, and chloride ion channel conductances, respectively, and a capacitor to account for the axon's membrane capacitance. We study the behavior of both ion channel conductivities and the circuit voltage, and we compare the results with those of the single channel, for a given quantum state of the source. It is remarkable that, in opposition to the single-channel model, we are able to reproduce the voltage spike in an adiabatic regime. Arguing that the circuit voltage is a quantum variable, we find a purely quantum-mechanical contribution in the system voltage's second moment. This work represents a complete study of the Hodgkin-Huxley model in the quantum regime, establishing a recipe for constructing quantum neuron networks with quantum state inputs. This paves the way for advances in hardware-based neuromorphic quantum computing, as well as quantum machine learning, which might be more efficient resource-wise.

scholarly journals The Intracellular Chloride Ion Channel Protein CLIC1 Undergoes a Redox-controlled Structural Transition

2003 ◽  
Vol 279 (10) ◽  
pp. 9298-9305 ◽  
Author(s):  
Dene R. Littler ◽  
Stephen J. Harrop ◽  
W. Douglas Fairlie ◽  
Louise J. Brown ◽  
Greg J. Pankhurst ◽  
...  
Keyword(s):  
Ion Channel ◽  
Structural Transition ◽  
Chloride Ion ◽  
Channel Protein ◽  
Intracellular Chloride

scholarly journals Computational Analysis of the Soluble Form of the Intracellular Chloride Ion Channel Protein CLIC1

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Peter M. Jones ◽  
Paul M. G. Curmi ◽  
Stella M. Valenzuela ◽  
Anthony M. George
Keyword(s):  
Ion Channel ◽  
Binding Site ◽  
Conformational Changes ◽  
Active Site ◽  
Bound States ◽  
Covalent Binding ◽  
Chloride Ion ◽  
Soluble Form ◽  
Active Site Cysteine ◽  
Dynamics Simulations

The chloride intracellular channel (CLIC) family of proteins has the remarkable property of maintaining both a soluble form and an integral membrane form acting as an ion channel. The soluble form is structurally related to the glutathione-S-transferase family, and CLIC can covalently bind glutathione via an active site cysteine. We report approximately 0.6 μs of molecular dynamics simulations, encompassing the three possible ligand-bound states of CLIC1, using the structure of GSH-bound human CLIC1. Noncovalently bound GSH was rapidly released from the protein, whereas the covalently ligand-bound protein remained close to the starting structure over 0.25 μs of simulation. In the unliganded state, conformational changes in the vicinity of the glutathione-binding site resulted in reduced reactivity of the active site thiol. Elastic network analysis indicated that the changes in the unliganded state are intrinsic to the protein architecture and likely represent functional transitions. Overall, our results are consistent with a model of CLIC function in which covalent binding of glutathione does not occur spontaneously but requires interaction with another protein to stabilise the GSH binding site and/or transfer of the ligand. The results do not indicate how CLIC1 undergoes a radical conformational change to form a transmembrane chloride channel but further elucidate the mechanism by which CLICs are redox controlled.

scholarly journals Molecular Cloning and Expression of a Chloride Ion Channel of Cell Nuclei

1997 ◽  
Vol 272 (19) ◽  
pp. 12575-12582 ◽  
Author(s):  
Stella M. Valenzuela ◽  
Donald K. Martin ◽  
Suzanne B. Por ◽  
Joan M. Robbins ◽  
Kristina Warton ◽  
...  
Keyword(s):  
Ion Channel ◽  
Molecular Cloning ◽  
Chloride Ion ◽  
Cloning And Expression ◽  
Cell Nuclei

Altered chloride ion channel kinetics associated with the ΔF508 cystic fibrosis mutation

Nature ◽  
1991 ◽  
Vol 354 (6354) ◽  
pp. 526-528 ◽  
Author(s):  
Wilfried Dalemans ◽  
Pascal Barbry ◽  
Guy Champigny ◽  
Sophie Jallat ◽  
Sophie Jallat ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Ion Channel ◽  
Chloride Ion ◽  
Channel Kinetics ◽  
Cystic Fibrosis Mutation ◽  
Ion Channel Kinetics

Effect of γ-vinyl γ -aminobutyric acid on the γ-aminobutyric acid receptor-coupled chloride ion channel in vesicles from the brain of the rat

1991 ◽  
Vol 30 (5) ◽  
pp. 423-427 ◽  
Author(s):  
Y. Suzuki ◽  
T. Mimaki ◽  
H. Arai ◽  
S. Okada ◽  
K. Kuriyama
Keyword(s):  
Ion Channel ◽  
Chloride Ion ◽  
Aminobutyric Acid ◽  
Acid Receptor ◽  
The Brain
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