Recognition: unknown
Neuronal electricality founded in murburn-thermodynamic principles: 1. Background and basic theoretical formulation
Pith reviewed 2026-05-10 11:22 UTC · model grok-4.3
The pith
Neuronal electrical activities arise from a unified reaction-transport-relaxation equation based on redox dynamics and thermodynamic gradients, providing an alternative to ion-centric models.
A machine-rendered reading of the paper's core claim, the machinery that carries it, and where it could break.
Core claim
By defining Electron Holding potential as a dimensionless state variable related to electron chemical potential, the authors combine local redox relaxation dynamics with thermodynamic gradient-driven transport to obtain a unified reaction-transport-relaxation equation. This single framework accounts for resting membrane potential, all-or-none excitability, stable action potential waveforms, and propagation along the axon length. Nonlinear kinetics in the redox system produce the threshold behaviors and waveforms observed in neurons, while accommodating physiological variability and connecting metabolic state to electrical output.
What carries the argument
The unified reaction-transport-relaxation equation, which integrates local redox relaxation dynamics with spatial transport driven by thermodynamic gradients, using Electron Holding potential as the central state variable.
Load-bearing premise
That the murburn concept of stochastic redox processes provides the foundational mechanisms allowing derivation of all neuronal electrical activities as an alternative to traditional ion gradient models.
What would settle it
An experiment that blocks key redox reactions in neurons while preserving ion gradients and checks whether electrical activity such as action potentials is abolished or persists as predicted by the new equation.
read the original abstract
Trans-membrane gradients and fluxes of cations (H+, Na+, K+, etc.) were deemed to be the rationale of electrical activities of aerobic cells/organelles, as per classical perceptions. Murburn concept (an umbrella of theorization based in stochastic redox processes) has afforded novel models for various metabolic, bioenergetic and electrophysiological outcomes. Herein, the foundational mechanistic formalisms for the electrical activities of neurons that lead signal relay along the axonal length are provided. Electron Holding potential (EHP), a dimensionless field/state variable (related logarithmically to electron chemical potential) is used to explain neuronal activity. By combining local redox relaxation dynamics with spatial transport driven by thermodynamic gradients, we derive a unified reaction-transport-relaxation equation that captures resting potential, excitability, waveform generation, and signal propagation within a single framework. Nonlinear local redox kinetics naturally give rise to threshold behavior, all-or-none responses, and stable spike waveforms. The framework accommodates known physiological variability and provides a direct bridge between metabolic/redox state and electrophysiological behavior. This work establishes a chemically grounded, non-circular alternative to ion-centric models and offers testable predictions for neuronal dynamics across biological systems. In the second part of this work, we compare the new theory with existing systems, provide further evidence, simulations and describe elaborate agendas for falsification and validation.
Editorial analysis
A structured set of objections, weighed in public.
Referee Report
Summary. The paper claims to establish foundational mechanistic formalisms for neuronal electrical activities based on murburn-thermodynamic principles. It introduces Electron Holding Potential (EHP) as a dimensionless field/state variable related logarithmically to electron chemical potential. By combining local redox relaxation dynamics with spatial transport driven by thermodynamic gradients, the authors assert derivation of a unified reaction-transport-relaxation equation that captures resting potential, excitability, waveform generation, and signal propagation within a single framework, offering a chemically grounded alternative to ion-centric models. Nonlinear local redox kinetics are said to naturally produce threshold behavior and stable spike waveforms, with the framework accommodating physiological variability and providing testable predictions. This is positioned as Part 1, with comparisons, simulations, and validation agendas reserved for Part 2.
Significance. If the central derivation proves sound and internally consistent, the work could provide a novel, non-circular bridge between metabolic/redox states and electrophysiological phenomena, potentially unifying explanations for resting potential, threshold responses, and propagation under a single thermodynamic-redox framework. It offers the prospect of direct, falsifiable links between cellular metabolism and signaling without reliance on separate ion-channel mechanisms, which could stimulate new experimental tests across neuronal systems if the formulation is made explicit and reproducible.
major comments (1)
- Abstract: The manuscript asserts that 'by combining local redox relaxation dynamics with spatial transport driven by thermodynamic gradients, we derive a unified reaction-transport-relaxation equation' that captures resting potential, excitability, waveform generation, and signal propagation. However, no explicit mathematical steps, assumptions, differential equations, boundary conditions, or the actual form of the unified equation are supplied. This derivation is load-bearing for every central claim in the paper; without it, the assertions about threshold behavior arising from nonlinear kinetics and the single-framework unification cannot be assessed for correctness or novelty.
minor comments (2)
- Abstract: The murburn concept is invoked as foundational without a brief self-contained definition or pointer to the key prior reference, reducing accessibility for readers encountering the framework for the first time.
- Abstract: The relation of EHP to electron chemical potential is described only as 'logarithmically related'; a short clarifying sentence on its definition and units would improve precision even at the abstract level.
Simulated Author's Rebuttal
We thank the referee for their careful and constructive review of our manuscript. We appreciate the recognition of the potential significance of the work and address the major comment in detail below. We are committed to improving the clarity and explicitness of the presentation.
read point-by-point responses
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Referee: Abstract: The manuscript asserts that 'by combining local redox relaxation dynamics with spatial transport driven by thermodynamic gradients, we derive a unified reaction-transport-relaxation equation' that captures resting potential, excitability, waveform generation, and signal propagation. However, no explicit mathematical steps, assumptions, differential equations, boundary conditions, or the actual form of the unified equation are supplied. This derivation is load-bearing for every central claim in the paper; without it, the assertions about threshold behavior arising from nonlinear kinetics and the single-framework unification cannot be assessed for correctness or novelty.
Authors: We acknowledge the referee's concern that the derivation requires greater explicitness for rigorous evaluation. In the manuscript's 'Basic Theoretical Formulation' section, we introduce the Electron Holding Potential (EHP) as a dimensionless state variable linked logarithmically to electron chemical potential, describe the local redox relaxation dynamics arising from stochastic murburn processes (yielding nonlinear kinetics), and combine these with spatial transport terms driven by thermodynamic gradients to arrive at the unified reaction-transport-relaxation equation. Key assumptions (such as local electroneutrality approximations, stochastic redox rate forms, and continuum limits for transport) are stated conceptually, and the resulting equation is presented in integrated form. However, we agree that a more detailed, step-by-step mathematical exposition—including the explicit differential equation, all assumptions, boundary conditions, and derivation sequence—would strengthen the work and enable direct assessment of novelty and internal consistency. In the revised manuscript, we will add an expanded subsection (or appendix) providing these explicit steps, the full mathematical form of the unified equation, and the boundary conditions employed. This revision will directly address the load-bearing nature of the derivation while preserving the Part 1 focus on foundational formulation (with quantitative simulations and comparisons reserved for Part 2). revision: yes
Circularity Check
No significant circularity detected in the derivation chain.
full rationale
The paper is explicitly Part 1 (background and basic theoretical formulation) and presents a high-level claim of deriving a unified reaction-transport-relaxation equation from local redox relaxation dynamics combined with thermodynamic spatial transport. No specific equations, definitions, or derivation steps are exhibited in the provided text that reduce by construction to the inputs (e.g., no self-definitional EHP or fitted parameters renamed as predictions). The murburn concept is invoked as an external foundational premise from prior work, but the current manuscript frames its contribution as a new formalization without load-bearing self-citations or ansatzes that collapse the central result. The text explicitly positions the framework as a non-circular alternative, and no internal reduction to fitted inputs or uniqueness theorems from the same authors is shown. This is the expected self-contained proposal for a theoretical formulation.
Axiom & Free-Parameter Ledger
axioms (1)
- domain assumption Stochastic redox processes from the murburn concept form the basis for neuronal electrical activities
invented entities (1)
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Electron Holding potential (EHP)
no independent evidence
Reference graph
Works this paper leans on
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[1]
Armstrong, C. M. (1971). Interact ion of tetraethylammonium ion derivatives with the potassium channels of giant axons. The Journal of General Physiology, 58(4), 413-437. DOI: 10.1085/jgp.58.4.413 Cahalan MD. (1978) Local anesthetic block of sodium channels in normal and pronase-treated squid giant axons. Biophysical Journal. 23(2):285-311. DOI: 10.1016/S...
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[2]
Carter BC, Bean BP. Sodium entry during action potentials of mammalian neurons: incomplete inactivation and reduced metabolic efficiency in fast -spiking neurons. Neuron. 2009 Dec 24;64(6):898-909. doi: 10.1016/j.neuron.2009.12.011. DeMaegd ML, Städele C, Stein W. Axonal Conduction Velocity Measurement. Bio Protoc. 2017 Mar 5;7(5):e2152. doi: 10.21769/Bio...
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[3]
33 Fatt, P.& Katz, B. (1953). The electrical properties of crustacean muscle fibres. Journal of Physiology, 120(1-2), 171–204. doi: 10.1113/jphysiol.1953.sp004884. FitzHugh, R. (1961). Impulses and physiological states in theoretical models of nerve membrane". Biophysical Journal, 1, 445–466. Gideon DA, Nirusimhan V , E JC, Sudarsha K, Manoj KM. (2022) Me...
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[4]
Origins–Sustenance–Termination– Evolution of Life
Jaeken L, Manoj KM (2025) Murburn B ioenergetics and “Origins–Sustenance–Termination– Evolution of Life”: Emergence of Intelligence from a Network of Molecules, Unbound Ions, Radicals and Radiations. International Journal of Molecular Sciences 26 (15),
2025
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[5]
Kandel, E. R., et al. (2021). Principles of Neural Science (6th ed.). McGraw Hill. Llinás, R., & Sugimori, M. (1980). Electrophysiological properties of Guillain-Barré Purkinje cells in vitro. Journal of Physiology, 305, 171-195. doi: 10.1113/jphysiol.1980.sp013358. Mangoni ME, Nargeot J. (2008) Genesis and regulation of the heart automaticity. Physiologi...
discussion (0)
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