scholarly journals Proton Quantum Tunneling: Influence and Relevance to Acidosis-Induced Cardiac Arrhythmias/Cardiac Arrest

2021 ◽  
Vol 28 (3) ◽  
pp. 400-441
Author(s):  
Omar Ababneh ◽  
Abdallah Barjas Qaswal ◽  
Ahmad Alelaumi ◽  
Lubna Khreesha ◽  
Mujahed Almomani ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Membrane Potential ◽  
Sodium Channels ◽  
Cardiac Arrhythmias ◽  
Quantum Tunneling ◽  
Membrane Depolarization ◽  
Cardiac Cells ◽  
Quantum Model ◽  
Quantum Conductance ◽  
Voltage Gated Sodium Channels

Acidosis and its associated pathologies predispose patients to develop cardiac arrhythmias and even cardiac arrest. These arrhythmias are assumed to be the result of membrane depolarization, however, the exact mechanism of depolarization during acidosis is not well defined. In our study, the model of quantum tunneling of protons is used to explain the membrane depolarization that occurs during acidosis. It is found that protons can tunnel through closed activation and inactivation gates of voltage-gated sodium channels Nav1.5 that are present in the membrane of cardiac cells. The quantum tunneling of protons results in quantum conductance, which is evaluated to assess its effect on membrane potential. The quantum conductance of extracellular protons is higher than that of intracellular protons. This predicts an inward quantum current of protons through the closed sodium channels. Additionally, the values of quantum conductance are influential and can depolarize the membrane potential according to the quantum version of the GHK equation. The quantum mechanism of depolarization is distinct from other mechanisms because the quantum model suggests that protons can directly depolarize the membrane potential, and not only through indirect effects as proposed by other mechanisms in the literature. Understanding the pathophysiology of arrhythmias mediated by depolarization during acidosis is crucial to treat and control them and to improve the overall clinical outcomes of patients.

scholarly journals Quantum Tunneling-Induced Membrane Depolarization Can Explain the Cellular Effects Mediated by Lithium: Mathematical Modeling and Hypothesis

Membranes ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 851
Author(s):  
Lubna Khreesha ◽  
Abdallah Barjas Qaswal ◽  
Baheth Al Omari ◽  
Moath Ahmad Albliwi ◽  
Omar Ababneh ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Quantum Tunneling ◽  
Lithium Concentration ◽  
Classical Model ◽  
Membrane Conductance ◽  
Membrane Depolarization ◽  
Quantum Model ◽  
Lithium Ions ◽  
Lithium Isotopes ◽  
Cellular Effects

Lithium imposes several cellular effects allegedly through multiple physiological mechanisms. Membrane depolarization is a potential unifying concept of these mechanisms. Multiple inherent imperfections of classical electrophysiology limit its ability to fully explain the depolarizing effect of lithium ions; these include incapacity to explain the high resting permeability of lithium ions, the degree of depolarization with extracellular lithium concentration, depolarization at low therapeutic concentration, or the differences between the two lithium isotopes Li-6 and Li-7 in terms of depolarization. In this study, we implemented a mathematical model that explains the quantum tunneling of lithium ions through the closed gates of voltage-gated sodium channels as a conclusive approach that decodes the depolarizing action of lithium. Additionally, we compared our model to the classical model available and reported the differences. Our results showed that lithium can achieve high quantum membrane conductance at the resting state, which leads to significant depolarization. The quantum model infers that quantum membrane conductance of lithium ions emerges from quantum tunneling of lithium through the closed gates of sodium channels. It also differentiates between the two lithium isotopes (Li-6 and Li-7) in terms of depolarization compared with the previous classical model. Moreover, our study listed many examples of the cellular effects of lithium and membrane depolarization to show similarity and consistency with model predictions. In conclusion, the study suggests that lithium mediates its multiple cellular effects through membrane depolarization, and this can be comprehensively explained by the quantum tunneling model of lithium ions.

scholarly journals Magnesium Ions Depolarize the Neuronal Membrane via Quantum Tunneling through the Closed Channels

2020 ◽  
Vol 2 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Abdallah Barjas Qaswal
Keyword(s):  
Membrane Potential ◽  
Quantum Tunneling ◽  
Magnesium Concentration ◽  
Resting Membrane Potential ◽  
Neuronal Membrane ◽  
Magnesium Ions ◽  
Quantum Conductance ◽  
Depolarization Effect ◽  
Bipolar Patients ◽  
Quantum Mechanical Approach

Magnesium ions have many cellular actions including the suppression of the excitability of neurons; however, the depolarization effect of magnesium ions seems to be contradictory. Thus several hypotheses have aimed to explain this effect. In this study, a quantum mechanical approach is used to explain the depolarization action of magnesium. The model of quantum tunneling of magnesium ions through the closed sodium voltage-gated channels was adopted to calculate the quantum conductance of magnesium ions, and a modified version of Goldman–Hodgkin–Katz equation was used to determine whether this quantum conductance was significant in affecting the resting membrane potential of neurons. Accordingly, it was found that extracellular magnesium ions can exhibit a depolarization effect on membrane potential, and the degree of this depolarization depends on the tunneling probability, the channels’ selectivity to magnesium ions, the channels’ density in the neuronal membrane, and the extracellular magnesium concentration. In addition, extracellular magnesium ions achieve a quantum conductance much higher than intracellular ones because they have a higher kinetic energy. This study aims to identify the mechanism of the depolarization action of magnesium because this may help in offering better therapeutic solutions for fetal neuroprotection and in stabilizing the mood of bipolar patients.

scholarly journals Tracking S4 movement by gating pore currents in the bacterial sodium channel NaChBac

2014 ◽  
Vol 144 (2) ◽  
pp. 147-157 ◽  
Author(s):  
Tamer M. Gamal El-Din ◽  
Todd Scheuer ◽  
William A. Catterall
Keyword(s):  
Membrane Potential ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Voltage Dependence ◽  
Periodic Paralysis ◽  
Membrane Potentials ◽  
Structural Basis ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Gating Charges

Voltage-gated sodium channels mediate the initiation and propagation of action potentials in excitable cells. Transmembrane segment S4 of voltage-gated sodium channels resides in a gating pore where it senses the membrane potential and controls channel gating. Substitution of individual S4 arginine gating charges (R1–R3) with smaller amino acids allows ionic currents to flow through the mutant gating pore, and these gating pore currents are pathogenic in some skeletal muscle periodic paralysis syndromes. The voltage dependence of gating pore currents provides information about the transmembrane position of the gating charges as S4 moves in response to membrane potential. Here we studied gating pore current in mutants of the homotetrameric bacterial sodium channel NaChBac in which individual arginine gating charges were replaced by cysteine. Gating pore current was observed for each mutant channel, but with different voltage-dependent properties. Mutating the first (R1C) or second (R2C) arginine to cysteine resulted in gating pore current at hyperpolarized membrane potentials, where the channels are in resting states, but not at depolarized potentials, where the channels are activated. Conversely, the R3C gating pore is closed at hyperpolarized membrane potentials and opens with channel activation. Negative conditioning pulses revealed time-dependent deactivation of the R3C gating pore at the most hyperpolarized potentials. Our results show sequential voltage dependence of activation of gating pore current from R1 to R3 and support stepwise outward movement of the substituted cysteines through the narrow portion of the gating pore that is sealed by the arginine side chains in the wild-type channel. This pattern of voltage dependence of gating pore current is consistent with a sliding movement of the S4 helix through the gating pore. Through comparison with high-resolution models of the voltage sensor of bacterial sodium channels, these results shed light on the structural basis for pathogenic gating pore currents in periodic paralysis syndromes.

Functional Assay of Voltage-Gated Sodium Channels Using Membrane Potential-Sensitive Dyes

2004 ◽  
Vol 2 (3) ◽  
pp. 260-268 ◽  
Author(s):  
John P. Felix ◽  
Brande S. Williams ◽  
Birgit T. Priest ◽  
Richard M. Brochu ◽  
Ivy E. Dick ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Sodium Channels ◽  
Functional Assay ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals FGF14 is a regulator of KCNQ2/3 channels

2016 ◽  
Vol 114 (1) ◽  
pp. 154-159 ◽  
Author(s):  
Juan Lorenzo Pablo ◽  
Geoffrey S. Pitt
Keyword(s):  
Membrane Potential ◽  
Sodium Channels ◽  
Molecular Mechanisms ◽  
Expression System ◽  
Cellular Mechanisms ◽  
Ankyrin G ◽  
Voltage Gated Sodium Channels ◽  
A Site ◽  
Interaction Surface ◽  
Insight Into

KCNQ2/3 (Kv7.2/7.3) channels and voltage-gated sodium channels (VGSCs) are enriched in the axon initial segment (AIS) where they bind to ankyrin-G and coregulate membrane potential in central nervous system neurons. The molecular mechanisms supporting coordinated regulation of KCNQ and VGSCs and the cellular mechanisms governing KCNQ trafficking to the AIS are incompletely understood. Here, we show that fibroblast growth factor 14 (FGF14), previously described as a VGSC regulator, also affects KCNQ function and localization. FGF14 knockdown leads to a reduction of KCNQ2 in the AIS and a reduction in whole-cell KCNQ currents. FGF14 positively regulates KCNQ2/3 channels in a simplified expression system. FGF14 interacts with KCNQ2 at a site distinct from the FGF14–VGSC interaction surface, thus enabling the bridging of NaV1.6 and KCNQ2. These data implicate FGF14 as an organizer of channel localization in the AIS and provide insight into the coordination of KCNQ and VGSC conductances in the regulation of membrane potential.

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