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On the Logical Bottom Line of Scientific Deduction from a Parts?per?Ten?Million Fluctuation

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2026-04-23

On the Logical Bottom Line of Scientific Deduction from a Parts?per?Ten?Million Fluctuation

Sun Zuodong

In the history of science, the greatness of many classic theories lies in their pioneering experiments, while controversies often hide at the most fundamental logical starting point.

The ionic theory of action potential established by Hodgkin, Huxley, and Katz in 1952 is built on a key premise: during an action potential, the membrane potential swings sharply from -60mV to +40mV, a massive fluctuation of nearly 100mV. Its main driving force is attributed to tiny changes in intracellular and extracellular ion concentrations caused by transmembrane ion flow.

Here lies a logically fundamental question: can a concentration fluctuation on the order of one part in ten million serve as a solid theoretical foundation to explain a potential change on the order of 100mV, in terms of physical dimensions and orders of magnitude?

The key is to convert this into actual ion numbers. During a single action potential, this “one part in ten million” concentration change corresponds to the transmembrane movement of thousands to tens of thousands of ions. Far from being negligible, the charges carried by these ions directly produce the large membrane potential fluctuation.

The core problem is that traditional theories attempt to use “concentration difference”, a macroscopic thermodynamic concept, to deduce and explain the instantaneous details of “potential change”, an electrodynamic phenomenon. This may involve logical detours and deviations. Rather than fixating on the tiny proportional change in concentration, we should directly examine and reconstruct the real motion trajectories of these thousands of key ions — how their transmembrane direction, speed, and quantity directly and correspondingly shape that classic potential waveform.

This is not a denial of the great experimental contributions of the pioneers, but a necessary examination of a basic logical link in theoretical deduction. If the starting point of the theory — explaining macroscopic potential changes with minute concentration variations — is strained in dimensional logic, the entire deductive system deserves more careful inspection.

Returning to the experimental waveform itself, a more straightforward explanatory path is: the symmetric rise and fall of the action potential may be driven directly by sodium ions as charge carriers undergoing an almost complete dynamic cycle of accelerated inward flow followed by symmetric accelerated outward flow. This more simply explains the rapid potential change and the smooth closed loop of the waveform.

Potassium ions, in this process, may mainly act as silent maintainers of the large concentration gradient (potential energy background) across the resting membrane. The resting potential may be closer to a steady state in which potassium ions remain relatively stationary on the inner side of the membrane.

Scientific progress lies not only in establishing equations, but also in constantly reviewing the most basic premises on which those equations are built. When theoretical deduction conflicts with intuitive physical scales, returning to the experimental origin and re-examining the real motion of key particles is an inevitable path for science to move forward.

This is not a rejection of history, but a necessary deepening and examination of classic theory driven by logic and empirical evidence.

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