Quantum Mechanical Aspects in the Pathophysiology of Neuropathic Pain.

Neuropathic pain is a challenging complaint for patients and clinicians since there are no effective agents available to get satisfactory outcomes even though the pharmacological agents target reasonable pathophysiological mechanisms. This may indicate that other aspects in these mechanisms should be unveiled to comprehend the pathogenesis of neuropathic pain and thus find more effective treatments. Therefore, in the present study, several mechanisms are chosen to be reconsidered in the pathophysiology of neuropathic pain from a quantum mechanical perspective. The mathematical model of the ions quantum tunneling model is used to provide quantum aspects in the pathophysiology of neuropathic pain. Three major pathophysiological mechanisms are revisited in the context of the quantum tunneling model. These include: (1) the depolarized membrane potential of neurons; (2) the cross-talk or the ephaptic coupling between the neurons; and (3) the spontaneous neuronal activity and the emergence of ectopic action potentials. We will show mathematically that the quantum tunneling model can predict the occurrence of neuronal membrane depolarization attributed to the quantum tunneling current of sodium ions. Moreover, the probability of inducing an ectopic action potential in the axons of neurons will be calculated and will be shown to be significant and influential. These ectopic action potentials are generated due to the formation of quantum synapses which are assumed to be the mechanism behind the ephaptic transmission. Furthermore, the spontaneous neuronal activity and the emergence of ectopic action potentials independently from any adjacent stimulated neurons are predicted to occur according to the quantum tunneling model. All these quantum mechanical aspects contribute to the overall hyperexcitability of the neurons and to the pathogenesis of neuropathic pain. Additionally, providing a new perspective in the pathophysiology of neuropathic pain may improve our understanding of how the neuropathic pain is generated and maintained and may offer new effective agents that can improve the overall clinical outcomes of the patients.

The Quantum Tunneling of Ions Model Can Explain the Pathophysiology of Tinnitus.

Tinnitus is a well-known pathological entity in clinical practice. However, the pathophysiological mechanisms behind tinnitus seem to be elusive and cannot provide a comprehensive understanding of its pathogenesis and clinical manifestations. Hence, in the present study, we explore the mathematical model of ions' quantum tunneling to propose an original pathophysiological mechanism for the sensation of tinnitus. The present model focuses on two major aspects: The first aspect is the ability of ions, including sodium, potassium, and calcium, to depolarize the membrane potential of inner hair cells and the neurons of the auditory pathway. This membrane depolarization is induced via the quantum tunneling of ions through closed voltage-gated channels. The state of membrane depolarization can be a state of hyper-excitability or hypo-excitability, depending on the degree of depolarization. Both of these states aid in understanding the pathophysiology of tinnitus. The second aspect is the quantum tunneling signals between the demyelinated neurons of the auditory pathway. These signals are mediated via the quantum tunneling of potassium ions, which exit to the extracellular fluid during an action potential event. These quantum signals can be viewed as a "quantum synapse" between neurons. The formation of quantum synapses results in hyper-excitability among the demyelinated neurons of the auditory pathway. Both of these aspects augment and amplify the electrical signals in the auditory pathway and result in a loss of the spatiotemporal fidelity of sound signals going to the brain centers. The brain interprets this hyper-excitability and loss of spatiotemporal fidelity as tinnitus. Herein, we show mathematically that the quantum tunneling of ions can depolarize the membrane potential of the inner hair cells and neurons of the auditory pathway. Moreover, we calculate the probability of action potential induction in the neurons of the auditory pathway generated by the quantum tunneling signals of potassium ions.

GABA Receptors Can Depolarize the Neuronal Membrane Potential via Quantum Tunneling of Chloride Ions: A Quantum Mathematical Study.

GABA (gamma-aminobutyric acid) receptors represent the major inhibitory receptors in the nervous system and their inhibitory effects are mediated by the influx of chloride ions that tends to hyperpolarize the resting membrane potential. However, GABA receptors can depolarize the resting membrane potential and thus can also show excitatory effects in neurons. The major mechanism behind this depolarization is mainly attributed to the accumulation of chloride ions in the intracellular compartment. This accumulation leads to increase in the intracellular chloride concentration and depolarize the Nernst potential of chloride ions. When the membrane potential is relatively hyperpolarized, this will result in a chloride efflux instead of influx trying to reach their depolarized equilibrium potential. Here, we propose different mechanism based on a major consequence of quantum mechanics, which is quantum tunneling. The quantum tunneling model of ions is applied on GABA receptors and their corresponding chloride ions to show how chloride ions can depolarize the resting membrane potential. The quantum model states that intracellular chloride ions have higher quantum tunneling probability than extracellular chloride ions. This is attributed to the discrepancy in the kinetic energy between them. At physiological parameters, the quantum tunneling is negligible to the degree that chloride ions cannot depolarize the membrane potential. Under certain conditions such as early neuronal development, gain-of-function mutations, stroke and trauma that can lower the energy barrier of the closed gate of GABA receptors, the quantum tunneling is enhanced so that the chloride ions can depolarize the resting membrane potential. The major unique feature of the quantum tunneling mechanism is that the net efflux of chloride ions is attained without the need for intracellular accumulation of chloride ions as long as the energy barrier of the gate is reduced but still higher than the kinetic energy of the chloride ion as a condition for quantum tunneling to take place.

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

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.

Mathematical Modeling of Ion Quantum Tunneling Reveals Novel Properties of Voltage-Gated Channels and Quantum Aspects of Their Pathophysiology in Excitability-Related Disorders.

Voltage-gated channels are crucial in action potential initiation and propagation and there are many diseases and disorders related to them. Additionally, the classical mechanics are the main mechanics used to describe the function of the voltage-gated channels and their related abnormalities. However, the quantum mechanics should be considered to unravel new aspects in the voltage-gated channels and resolve the problems and challenges that classical mechanics cannot solve. In the present study, the aim is to mathematically show that quantum mechanics can exhibit a powerful tendency to unveil novel electrical features in voltage-gated channels and be used as a promising tool to solve the problems and challenges in the pathophysiology of excitability-related diseases. The model of quantum tunneling of ions through the intracellular hydrophobic gate is used to evaluate the influence of membrane potential and gating free energy on the tunneling probability, single channel conductance, and quantum membrane conductance. This evaluation is mainly based on graphing the mathematical relationships between these variables. The obtained mathematical graphs showed that ions can achieve significant quantum membrane conductance, which can affect the resting membrane potential and the excitability of cells. In the present work, quantum mechanics reveals original electrical properties associated with voltage-gated channels and introduces new insights and implications into the pathophysiology of excitability- related disorders. In addition, the present work sets a mathematical and theoretical framework that can be utilized to conduct experimental studies in order to explore the quantum aspects of voltage-gated channels and the quantum bioelectrical property of biological membranes.

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

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.

Lithium Stabilizes the Mood of Bipolar Patients by Depolarizing the Neuronal Membrane Via Quantum Tunneling through the Sodium Channels.

OBJECTIVE: Lithium is used as first line in treating bipolar patients to stabilize their mood. However, the exact mechanism of lithium is not yet established. One of the proposed mechanisms is that lithium depolarizes the hyperpolarized neuronal membrane of bipolar patients bringing it back to the normal potential. On the other hand, the only way that lithium causes significant therapeutic depolarization is to have a membrane conductance that must be at least an order of magnitude higher than that for sodium but this is not achieved since both; lithium and sodium have the same conductance because the membrane channels are selective for them approximately by the same degree. So, this study aimed to explain how lithium could achieve higher conductance than sodium. METHODS: The idea of quantum tunneling through closed channels was used in a way to calculate the tunneling probability and the quantum conductance for lithium ions. RESULTS: It was found that lithium could achieve higher conductance than sodium because it has a smaller mass than sodium making lithium to have higher probability of tunneling and consequently higher conductance through channels and membrane. CONCLUSION: Lithium tunneling model provides a reasonable explanation for the therapeutic depolarization effect of lithium. This model is experimentally testable to prove the tunneling effect of ions through the closed channels and to show the variations of quantum conductance between ions according to their mass.

Role of Potassium Ions Quantum Tunneling in the Pathophysiology of Phantom Limb Pain.

1) Background: multiple theories were proposed to explain the phenomenon of phantom limb pain (PLP). Nevertheless, the phenomenon is still shrouded in mystery. The aim of this study is to explore the phenomenon from a new perspective, where quantum tunneling of ions, a promising field in medical practice, might play a major role. 2) Methods: investigators designed a quantum mathematical model based on the Schrödinger equation to examine the probability of potassium ions quantum tunneling through closed membrane potassium channels to the inside of phantom axons, leading to the generation of action potential. 3) Results: the model suggests that the probability of action potential induction at a certain region of the membrane of phantom neurons, when a neuron of the stump area is stimulated over 1 mm2surface area of the membrane available for tunneling is 1.04 × 10-2. Furthermore, upon considering two probabilities of potassium channelopathies, one that decreased the energy of the barrier by 25% and another one by 50%, the tunneling probability became 1.22 × 10-8 and 3.86 × 10-4, respectively. 4) Conclusion: quantum models of potassium ions can provide a reliable theoretical hypothesis to unveil part of the ambiguity behind PLP.