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The model needs to be discarded, not protected

Posted by Gregorio on 21 Jan 2009 at 00:06 GMT

It is stated that in 1952 "Hodgkin and Huxley described the underlying mechanism for the firing of action potentials through which information is propagated in the nervous system." John Eccles was part of this formulation, and the three received a Nobel in 1963 for the model known as the ionic channel model of nerve impulse propagation. In 1993 Eccles abjured the model as inadequate for information encoding in a system said to involve information processing. In 1994 [Reinventing the Future, Bass] Bert Sakmann, who received a Nobel in 1991 for his invention of patch clamping, a technique for studying the electrical dynamics of individual ion channels, averred that the meaningless of the individual nerve impulse was not important, that, through frequency encoding, information was transmitted by variation in the rates of meaningless impulses. When asked to elaborate upon frequency encoding and how the information was translated, Sakmann responded it was a mystery. Sakmann insisted, however, that the electrical activity of the cell and body did not generally involve electrons, and that this indeed was hard to understand. Sakmann finished the interview that, after a period of retirement, he had returned to the study of signal transmission, and that people were still asking the same question.

The alleged mechanism described by Hodgkin and Huxley was an elaboration upon the hypothesis of Julius Bernstein [1902] that related Nernst voltages to electrical voltages, despite that Nernst himself made clear in 1888 his equation was not about electromagnetism or electrical pressure, but was instead about entropic pressure. Nernst was about thermodynamics.

Hodgkin and Huxley's model was a spurious attempt to model electrical activities in terms of thermodynamics, on the basis of ion concentration gradients. Bertil Hille [Ion Channels of Excitable Membranes, 1991] claimed they had it right, and that this form of electricity was like the flow of fluids in small tubes. Hille speaks of ionic currents carried by water. No tests were ever done to examine for whether the movement of charge carried by ion current induced a magnetic field, not in 1902, not in 1952, not in 1963, never.

In 1978 Peter Mitchell received a Nobel for his elaboration on the Hodgkin-Huxley model, that led to the supplementation of sodium pumps, potassium pumps, and the other machinery of thermodynamic electricity, with proton pumps and chemiosmosis. His elaboration involved the conflation of pH gradients with electrical pressures, saying that a pH gradient of 3.5 had a value of 210 mV. His account did not allow for the gradient to be on either side of a pH value of 7, however. Instead it had to span that value, involving acid-base reactions. His account therefore eliminated the relevance of the mathematics of Nernst decisively. Those mathematics were not about pH and acid-base reactions, and were equally valid for all ranges of pH number, above and below 7, since what was dealt with was concentrations.

Moreover, Mitchell and his followers committed a serious methodological error in that two incommensurable theories were combined, electromagnetism and acidity, even on irrelevant mathematical foundations. The methodological error was institutionalized in the idea that bioelectricity (like that in the nervous system) involved THE SEPARATION OF CHARGE, with negative and positive on opposite sides of a membrane, or acids and bases separated. Electrons and electricity, does not have a positive charge. Despite this Hille claimed [1991] the Hodgkin-Huxley model was based almost entirely on electrical measurements.

We now have the present authors claiming that the deviations of the data from the predictions of the Hodgkin-Huxley model might not be so at odds with the model if the presumption is made ion channels open cooperatively. They assert the deviations hinge on measurement of noise strength, something pertinent to and signaling ionic cooperation, perhaps. They don't question the model at all, but seek only ways to render it more consonant with the data. They too cite electrical measurements, and regard ion currents as having gaussian reality, though in the realm of biophysics. Electrical ion currents are not to be found in the physical sciences, where the movement of ions is R, not I, in Ohm's Law, when electricity is involved. The model has problems more fundamental than the authors can imagine. Instead they envision new ion-channel characteristics to supplement those like 'voltage-gating', and never envision that channel as an electrochemical salt bridge.

Voltage-gating is the name given to the assumption of values for membrane permeability in the Goldman Equation. The Goldman Equation is an elaboration on the Nernst equation necessitated by the discovery that cell voltages measured did not agree with cell voltages calculated according to Nernst. This minor embarrassment, acknowledged in Koester's "Cell Membrane Voltages" [Principles of Neural Science, 1991], and illustrated there with a graph showing measured voltages plotted against Nernst voltages for potassium ion concentrations. In the illustration the two lines intersect once, and deviate on either side. Koester claimed cell voltages measured deviated because other ions besides those for potassium were present, throwing off the reading. Thus - the Goldman Equation with its assumptions about membrane permeability or gating, assumptions that saved the model from the conflicting data.

The authors of this paper are doing the same thing.