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Membrane Potential: A Critical Reassessment of Pump Theory and an Electrostatic Adsorption Model

Publié
Serveur de preprints
Preprints.org
DOI
10.20944/preprints202603.0814.v1

The membrane pump theory (MPT) attributes the resting membrane potential of neurons to ionic diffusion driven by transmembrane concentration gradients, maintained by the Na,K-ATPase. Despite decades of dominance, this model harbours fundamental thermodynamic, kinetic, and geometric inconsistencies that have remained unaddressed in mainstream biophysics. We present a systematic quantitative critique across five independent axes: (1)~the electrostatic force exceeds the diffusive force by ∼\sim300-fold under physiological conditions; (2)~the peri-axonal space contains 10--100×\times fewer ions than required by channel-based models; (3)~the Na,K-ATPase carries an energy deficit of ∼\sim26\% per cycle and operates 5000×\times too slowly to compensate measured leak fluxes; (4)~the Nernst and Goldman--Hodgkin--Katz equations are applied outside their domain of validity; and (5)~cell geometry invalidates plane-membrane approximations. In contrast, direct experimental evidence (Tamagawa experiment) demonstrates that a potential of ≈−40\approx -40\,mV arises from fixed negative charges alone, without any ionic gradient. We formalise this result within a Poisson--Boltzmann/Grahame electrostatic framework, supplemented by Ling's ion adsorption model and Manoj's murburn concept, and obtain Δψ≈−65\Delta\psi \approx -65 to −85-85\,mV from first principles. Four specific experimental predictions distinguish the model from MPT.

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