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.

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.

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.

MODELING OF WOLFF–PARKINSON–WHITE SYNDROME

2003 ◽  
Vol 13 (12) ◽  
pp. 3827-3834
Author(s):  
ROBERT HINCH
Keyword(s):  
Asymptotic Analysis ◽  
Ion Channel ◽  
Sodium Channel ◽  
Channel Model ◽  
Accessory Pathway ◽  
Simplified Model ◽  
Channel Kinetics ◽  
White Syndrome ◽  
Channel Density ◽  
Wolff Parkinson White Syndrome

Wolff–Parkinson–White syndrome is a disease where an arrhythmia is caused by the ventricles being electrically excited by an additional accessory pathway that links the atria to the ventricles. The spread of the activation wave from this pathway to the ventricles is modeled using a simplified model of Hodgkin–Huxley sodium channel kinetics, in a two ion-channel model. The model is investigated both analytically (using an asymptotic analysis) and numerically, and both methods are shown to give the same result. It is found that for a given width of the accessory pathway, there is a critical sodium channel density needed for the activation wave to spread from the pathway to the tissue. This result provides an explanation for the success of class-I anti-arrhythmic drugs in treating Wolff–Parkinson–White syndrome.

scholarly journals On the Importance of Atomic Fluctuations, Protein Flexibility, and Solvent in Ion Permeation

2004 ◽  
Vol 124 (6) ◽  
pp. 679-690 ◽  
Author(s):  
Toby W. Allen ◽  
O.S. Andersen ◽  
Benoit Roux
Keyword(s):  
Ion Channel ◽  
Protein Function ◽  
Channel Model ◽  
Protein Structures ◽  
Thermal Fluctuations ◽  
Model Parameters ◽  
Ion Permeation ◽  
Model Calculations ◽  
Channel Interactions ◽  
Solvent Molecules

Proteins, including ion channels, often are described in terms of some average structure and pictured as rigid entities immersed in a featureless solvent continuum. This simplified view, which provides for a convenient representation of the protein's overall structure, incurs the risk of deemphasizing important features underlying protein function, such as thermal fluctuations in the atom positions and the discreteness of the solvent molecules. These factors become particularly important in the case of ion movement through narrow pores, where the magnitude of the thermal fluctuations may be comparable to the ion pore atom separations, such that the strength of the ion channel interactions may vary dramatically as a function of the instantaneous configuration of the ion and the surrounding protein and pore water. Descriptions of ion permeation through narrow pores, which employ static protein structures and a macroscopic continuum dielectric solvent, thus face fundamental difficulties. We illustrate this using simple model calculations based on the gramicidin A and KcsA potassium channels, which show that thermal atomic fluctuations lead to energy profiles that vary by tens of kcal/mol. Consequently, within the framework of a rigid pore model, ion-channel energetics is extremely sensitive to the choice of experimental structure and how the space-dependent dielectric constant is assigned. Given these observations, the significance of any description based on a rigid structure appears limited. Creating a conducting channel model from one single structure requires substantial and arbitrary engineering of the model parameters, making it difficult for such approaches to contribute to our understanding of ion permeation at a microscopic level.

Thermal Hydraulic Studies of a Fluoride Salt Cooled High Temperature Test Reactor With Different CFD Methods

2014 ◽  
Author(s):  
Chenglong Wang ◽  
Yao Xiao ◽  
Jianjun Zhou ◽  
Dalin Zhang ◽  
Suizheng Qiu ◽  
...  
Keyword(s):  
High Temperature ◽  
Channel Model ◽  
Single Channel ◽  
Fluoride Salt ◽  
Applied Physics ◽  
Local Flow ◽  
Single Channel Analysis ◽  
Test Reactor ◽  
Safety Operation ◽  
Temperature Test

The Fluoride-salt-cooled High temperature Reactor (FHR) is new reactor concept-about a decade old which is mainly on going in China and U.S. The preliminary thermal-hydraulic studies of the Fluoride salt cooled High temperature Test Reactor (FHTR) is necessary for the development of the FHR technology. In this paper, the thermal-hydraulics of FHTR (also called TMSR-SF) designed by Shanghai Instituted of Applied Physics (SINAP) is studied in different power modes. The temperature distributions of the coolant and the fuel pebble are obtained using a steady-state thermal-hydraulic analysis code for FHR. The comprehensive local flow and heat transfer are investigated by computational fluid dynamics (CFD) for the locations where may have the maximum pebble temperature based on the results from single channel analysis. The profiles of temperature, velocity, pressure and Nu of the coolant on the surface of the pebble as well as the temperature distribution of a fuel pebble are obtained and analyzed. Numerical results showed that the results of 3-D simulation are in reasonable agreement with that of single channel model and also illustrated safety operation of the preliminary designed TMSR-SF in different power mode.

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 TOK Homologue in Neurospora crassa: First Cloning and Functional Characterization of an Ion Channel in a Filamentous Fungus

2003 ◽  
Vol 2 (1) ◽  
pp. 181-190 ◽  
Author(s):  
Stephen K. Roberts
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Neurospora Crassa ◽  
Filamentous Fungus ◽  
Single Channel ◽  
Functional Characterization ◽  
Reversal Potential ◽  
Channel Activity ◽  
Biophysical Properties ◽  
Patch Clamp Technique

ABSTRACT In contrast to animal and plant cells, very little is known of ion channel function in fungal physiology. The life cycle of most fungi depends on the “filamentous” polarized growth of hyphal cells; however, no ion channels have been cloned from filamentous fungi and comparatively few preliminary recordings of ion channel activity have been made. In an attempt to gain an insight into the role of ion channels in fungal hyphal physiology, a homolog of the yeast K+ channel (ScTOK1) was cloned from the filamentous fungus, Neurospora crassa. The patch clamp technique was used to investigate the biophysical properties of the N. crassa K+ channel (NcTOKA) after heterologous expression of NcTOKA in yeast. NcTOKA mediated mainly time-dependent outward whole-cell currents, and the reversal potential of these currents indicated that it conducted K+ efflux. NcTOKA channel gating was sensitive to extracellular K+ such that channel activation was dependent on the reversal potential for K+. However, expression of NcTOKA was able to overcome the K+ auxotrophy of a yeast mutant missing the K+ uptake transporters TRK1 and TRK2, suggesting that NcTOKA also mediated K+ influx. Consistent with this, close inspection of NcTOKA-mediated currents revealed small inward K+ currents at potentials negative of EK. NcTOKA single-channel activity was characterized by rapid flickering between the open and closed states with a unitary conductance of 16 pS. NcTOKA was effectively blocked by extracellular Ca2+, verapamil, quinine, and TEA+ but was insensitive to Cs+, 4-aminopyridine, and glibenclamide. The physiological significance of NcTOKA is discussed in the context of its biophysical properties.

scholarly journals A New Neuron Ion Channel Model Under Time Varying Input Currents

2021 ◽  
Vol 1999 (1) ◽  
pp. 012127
Author(s):  
Ahmed Mahmood Khudhur ◽  
Ahmed M Shano ◽  
Abdul Salam Hassan Abbas
Keyword(s):  
Ion Channel ◽  
Channel Model ◽  
Time Varying ◽  
Ion Channel Model

Blocking Mechanisms of Ketamine and Its Enantiomers in Enzymatically Demyelinated Peripheral Nerve as Revealed by Single-channel Experiments

1997 ◽  
Vol 86 (2) ◽  
pp. 394-404 ◽  
Author(s):  
Michael E. Brau ◽  
Frank Sander ◽  
Werner Vogel ◽  
Gunter Hempelmann
Keyword(s):  
Potassium Channels ◽  
Peripheral Nerve ◽  
Ion Channel ◽  
Single Channel ◽  
Resting Potential ◽  
K Channel ◽  
Resting Membrane Potential ◽  
Na Channel ◽  
Ic50 Values ◽  
Sodium And Potassium

Background Ketamine shows, besides its general anesthetic effect, a local anesthetic-like action that is due to blocking of peripheral nerve sodium currents. In this study, the stereoselectivity of the blocking effects of the ketamine enantiomers S(+) and R(-) was investigated in sodium and potassium channels in peripheral nerve membranes. Methods Ion channel blockade of ketamine was investigated in enzymatically dissociated Xenopus sciatic nerves in multiple-channel and in single-channel outside-out patches. Results Concentration-effect curves for the Na+ peak current revealed half-maximal inhibiting concentrations (IC50) of 347 microM and 291 microM for S(+) and R(-) ketamine, respectively. The potential-dependent K+ current was less sensitive than the Na+ current with IC50 values of 982 microM and 942 microM. The most sensitive ion channel was the flickering background K+ channel, with IC50 values of 168 microM and 146 microM for S(+) and R(-) ketamine. Competition experiments suggest one binding site at the flicker K+ channel, with specific binding affinities for each of the enantiomers. For the Na+ channel, the block was weaker in acidic (pH = 6.6) than in neutral (pH = 7.4) and basic (pH = 8.2) solutions; for the flicker K+ channel, the block was weaker in acidic and stronger in basic solutions. Conclusions Ketamine blockade of sodium and potassium channels in peripheral nerve membranes shows no stereoselectivity except for the flicker K+ channel, which showed a very weak stereoselectivity in favor of the R(-) form. This potential-insensitive flicker K+ channel may contribute to the resting potential. Block of this channel and subsequent depolarization of the resting membrane potential leads, besides to direct Na+ channel block, to inexcitability via Na+ channel inactivation.

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