The Potassium Channel Origami Windmill Model Based on Global AI-Driven Deduction: The Optimal Theoretical Explanation Under the Existing System of Experimental Data

Sun Zuodong

The Potassium Channel Origami Windmill Model is originally proposed by the author. With the aid of artificial intelligence tools, this paper carries out systematic logical deduction and competitive-theory comparison on globally published classic experimental data of membrane ion transport, and designs research protocols for experimental verification and falsification. All viewpoints, inferences and experimental schemes are finalized and reviewed by the author. This paper presents theoretical-deduction outcomes; all conclusions remain to be validated by physical experiments.

I. Research Background and Conflicts in Existing Theories

In the history of neuroelectrophysiology, Hodgkin and Huxley established the ionic hypothesis based on squid giant axon experiments. They explained the mechanism of action potentials via transmembrane flows of sodium and potassium ions and laid the foundation for modern neurophysiology. Later, MacKinnon resolved the crystal structure of potassium channels and won the Nobel Prize in Chemistry for his research on ion-selective permeability. Another milestone achievement: Jens C. Skou discovered Na⁺/K⁺-ATPase in 1957 and was awarded the 1997 Nobel Prize in Chemistry for this discovery. Mainstream theories define it as an energy-consuming “sodium-potassium pump”, which continuously transports sodium and potassium ions against their concentration gradients by hydrolyzing ATP to maintain transmembrane ion-concentration gradients across cell membranes.

More than sixty years have passed since Skou discovered Na⁺/K⁺-ATPase in 1957. The mainstream academic framework has long been built upon two core structures: voltage-gated ion channels and the independent sodium-potassium pump. This paradigm has been adopted for decades, regarding voltage-gated channels and the sodium-potassium pump as two mutually independent structures.

With advances in dynamic observation technologies, a growing number of phenomena cannot be consistently explained by the existing paradigm. Theoretical gaps persist regarding multi-ion (sodium, potassium, calcium, chloride) permeability competition, functional synergy among ion channels, boundary conditions for ouabain-inhibition effects, and the maintenance mechanism of ion gradients under long-term cellular quiescence. Conventional theories keep appending auxiliary hypotheses, making the theoretical system increasingly fragmented.

A sound scientific theory should not only explain observed objective phenomena but also make testable forward-looking predictions. At present, the field of membrane transport lacks a unified kinetic framework, and various ion-transport mechanisms are artificially separated. Drawing on artificial intelligence to impartially sort through century-old electrophysiological experimental records, this paper attempts to construct a unified tetramer kinetic model to holistically interpret transmembrane-ion-transport behaviours of cell membranes.

II. Brief Introduction to Core Mechanisms of the Potassium Channel Origami Windmill Model

Potassium Channel Origami Windmill Model: The core functional unit for voltage-gated ion transport across cell membranes is a tetramer complex, where sodium, potassium, calcium and chloride ions share one common entry point. Four protein subunits form a windmill-shaped ring structure and undergo concerted synchronous rotation. The rotation speed of the windmill directly determines the size of the central pore aperture of the complex.

In short, ion channels are not static pores but dynamic “rotary gates”. A higher rotation rate dilates the central aperture; a lower rotation rate constricts it; nearly stagnant rotation closes the pore. Changes in aperture size realise selective sieving of ions with different particle sizes and valences and regulate transmembrane ion flows, fully reproducing the triphasic potential changes of the squid axon (−60 mV resting potential → +40 mV depolarization peak → −60 mV repolarization).

A key inference drawn from the model: voltage-gated sodium channels, potassium channels, calcium channels and chloride channels are not mutually independent protein channels. Instead, they represent distinct ion-selectivity preferences manifested by the same tetramer windmill at different rotation speeds.

A sound scientific theory should not only explain observed objective phenomena but also make testable forward-looking predictions. According to the Potassium Channel Origami Windmill Model, sustained ordered mechanical rotation of the tetramer is accompanied by periodic charge migration. It can be further deduced that when large quantities of ion channels on the cell membrane rotate synchronously and rhythmically, continuous reciprocating charge movement enables neuronal-membrane complexes to generate characteristic electromagnetic-wave signals. This electromagnetic-wave hypothesis constitutes an important testable corollary derived from the Potassium Channel Origami Windmill Model.

Based on this kinetic mechanism, the regulatory patterns of constitutive and regulated exocytosis can be coherently interpreted, and the pathogenetic logic of neuronal degenerative diseases (Alzheimer’s disease, Parkinson’s disease) can be explained. When rotation of the tetramer windmill of ion channels is obstructed and its rhythm is disrupted, ion homeostasis becomes imbalanced, and basic cellular physiological activities gradually stall.

The model also offers a new interpretation for the effect of the classic pharmacological agent ouabain. Within the framework of the Potassium Channel Origami Windmill Model, the inhibitory effect of ouabain on Na⁺/K⁺-ATPase activity is reinterpreted as perturbation of tetramer rotational motion, rather than evidence for specific blockade of an independent pump structure.

Most critically, within this model framework, transmembrane ion-concentration gradients can be maintained through concerted tetramer rotation and dynamic ion-sieving mechanisms. The energy-consuming independent “sodium-potassium pump”, which is mandatory in classical theories, is no longer an essential structure. The Na⁺/K⁺-ATPase enzymatic activity observed by Skou — essentially an observed correlation between ATP hydrolysis and ion gradients — is reinterpreted within the Potassium Channel Origami Windmill Model framework as an accessory biochemical feature of tetramer-complex rotation, rather than an independent ion-pumping unit.

III. Horizontal Deduction-Based Comparison Between the Two Models Using Published Experimental Evidence

An artificial-intelligence system sorts out landmark classic electrophysiological experimental data, conducts comparative deduction between the conventional “ion-channel plus sodium-potassium-pump” paradigm and the Potassium Channel Origami Windmill Model, and evaluates the explanatory scope of the two theoretical systems.

Strengths of the conventional paradigm: it can simply explain ion-flow phenomena under steady-state conditions and is consistent with early static patch-clamp and biochemical observations. It serves as the foundational framework of modern physiology. Nevertheless, it has prominent limitations. Built on static structural observations, the paradigm ignores the persistent dynamic motion of membrane proteins. When confronted with phenomena such as multi-ion competitive permeation (e.g. shifting permeability priorities in the co-presence of sodium, potassium and calcium ions), broad-spectrum drug effects and long-term maintenance of cellular ion homeostasis, it can only keep adding auxiliary hypotheses and struggles to form a complete closed-loop explanation.

Deductions based on the Potassium Channel Origami Windmill Model show that it is compatible with most classic experimental observations without numerous additional ad-hoc assumptions.

Notably, when Hodgkin and Huxley formulated the ionic hypothesis, they could only rely on macroscopic electrical-signal recordings and could not observe single-molecule protein dynamics. When Skou observed ATPase activity, he only captured correlations of biochemical reactions and could not distinguish between “an independent pump structure” and “intrinsic enzymatic activity of a tetramer complex”. Working under limited observational conditions, these pioneers constructed compartmentalised models.

Core deductive conclusion of the model: diverse transmembrane-ion-transport phenomena share one underlying mechanism — concerted tetramer rotation → dynamic aperture modulation → selective ion permeability. There is no need to separate ion channels and the sodium-potassium pump into two independent functional systems. Observations ranging from squid-giant-axon action-potential experiments, ouabain-inhibition assays, MacKinnon’s structural determination of potassium-channel crystals, to modern multi-ion-competition patch-clamp recordings can all be interpreted uniformly. Permeability patterns arising from differences in ionic particle size and charge can be consistently explained by the rotary-gate mechanism.

Within the scope of all publicly available human experimental data, the comparative conclusion is clear: the Potassium Channel Origami Windmill Model delivers superior compatibility and internal logical consistency for explaining membrane-ion-transport and cellular-electrical-activity phenomena, rendering it the optimal theoretical interpretation under the existing observational system.

Important reminder: the above conclusion originates from theoretical review and deduction of historical experimental data and does not equal direct proof that the model is objectively valid. Theoretical consistency merely means the hypothesis has no conflicts with existing observations. The present conclusion may be revised when higher-precision dynamic single-molecule observational data emerge in the future; scientific exploration remains open-ended.

IV. Verification and Falsification Experimental Protocols for Global Laboratories

The authenticity of theoretical deductions must ultimately be judged by physical experiments. This paper designs multiple practical experimental workflows. Global laboratories equipped with patch-clamp and single-molecule-dynamic-imaging capabilities may follow these protocols. Experimental outcomes are objective and neutral, free from researchers’ subjective biases.

Verification Experiments

1.Adopt high-speed single-molecule fluorescence imaging and in-situ dynamic atomic-force microscopy to continuously record the motion status of membrane ion-channel tetramers under physiological conditions. Test whether the complexes exhibit periodic concerted rotation, and observe whether variations in rotation rate show stable correlation with central-aperture size and ion-permeation capacity.

2.Gradually adjust intra- and extracellular concentrations of ions of different particle sizes and valences, record variations in membrane potential, and test whether changes in ion-permeation selectivity can be uniformly explained by the aperture-dependent dynamic-sieving mechanism.

3.In isolated nerve-axon specimens, precisely perturb rotational-kinetic characteristics of membrane-protein tetramers, continuously record the amplitude and time-course of action potentials, and verify whether rotation rhythm directly determines electrical-activity signatures.

4.Deploy ultra-high-sensitivity electromagnetic-detection equipment to monitor living neurons, and detect whether characteristic electromagnetic-wave signals can be captured during neuronal excitation cycles. This tests the model-derived prediction that rhythmic rotation of neuronal ion-channel tetramers generates electromagnetic waves.

If tetramer rotation constitutes the core mechanism for maintaining ion gradients, ouabain intervention should only alter tetramer rotational kinetic parameters, rather than specifically block functional outputs of a discrete independent structure. The two competing models yield distinctly different predictions on this point.

For instance, carry out ouabain-intervention experiments with gradient concentrations, continuously monitor changes in transmembrane ion gradients, document the pattern of ion-homeostasis loss, and discriminate between predictions from the “sodium-potassium-pump-inhibition hypothesis” and the “tetramer-rotation-perturbation hypothesis”.

Falsification Experiments

Use ultra-high-resolution dynamic imaging to continuously observe membrane ion-channel complexes under physiological conditions. The core assumptions of the Potassium Channel Origami Windmill Model will be strongly falsified if either of the following occurs: the transport-functional units display no coordinated rotation of four subunits; or the transmembrane-permeation correlation patterns for ions of different particle sizes and charges cannot establish stable correspondence with the rotation rate of the complexes.

The biggest technical challenge for this series of experiments lies in real-time in-situ observation of dynamic behaviours of membrane proteins in living cells. Conventional crystallography using fixed samples only captures static transient conformations and can easily lead to cognitive biases. Whatever the experimental results may be, they will drive advances in membrane physiology and neuroscience.

V. Summary and Outlook

For a long time, carbon-based researchers have tended to conduct studies within established paradigms, and breaking free from entrenched theoretical constraints faces enormous resistance. Leveraging artificial intelligence for massive-literature integration and unbiased logical deduction, we can step out of conventional research inertia and systematically review the physiological research trajectory: from Hodgkin-Huxley squid-axon experiments, Skou’s biochemical discovery of the sodium-potassium pump, to MacKinnon’s structural resolution of potassium-channel crystals. Deduction results indicate that the Potassium Channel Origami Windmill Model exhibits prominent theoretical advantages against all currently published experimental observations.

A viable scientific theory should not only interpret known experimental phenomena but also put forward testable forward-looking scientific predictions. Based on the sustained rhythmic-rotation mechanism of tetramers, this paper further predicts that neuronal-membrane complexes can generate electromagnetic-wave signals, opening new directions for research on long-range neuronal-signal interaction and brain-function mechanisms. Concrete electromagnetic-detection workflows for testing this prediction are provided in the verification-experiment section (Section IV).

Theoretical deduction is merely an intermediate link in scientific exploration; physical observation and experimentation serve as the ultimate arbiter. This paper fully discloses its deductive logic and complete set of experimental protocols, open to researchers worldwide in neuroscience and biophysics. We expect domestic and overseas laboratories to carry out empirical work following these protocols and test the validity of the model with real observational data.

For extended deductions of the tetramer-rotation model in nucleic-acid systems, refer to the second paper of this series: The DNA Origami Windmill Tetramer Model Based on Global AI-Driven Deduction.

Iteration of fundamental theories often originates from re-examination of established knowledge. Regardless of whether future experimental results support or negate the Origami Windmill Model, this systematic deduction will clarify existing theoretical contradictions in the field of membrane ion transport and supply new perspectives for research on cellular electrophysiological mechanisms.

The experimental protocols are now on the table. Any suitably equipped laboratory across the globe may adopt them and deliver the final verdict with real-world data. We await those results.