Evidence for excitability of Schwann cells

Evidence for excitability of Schwann cells | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 29 August 2025 V1 Latest version Share on Evidence for excitability of Schwann cells Author : Wolfgang Herzberg 0009-0002-8056-3980 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.175647904.43087524/v1 178 views 106 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract An old debate about the excitability of the neural myelin sheath, which was fought in Europe between the world wars of the last century, has been settled. Schwann cells are active players in excitation conduction! A study by G. David provides sufficient evidence for this.1 This means that the membranes of the myelin sheath are excitable, i.e., possess voltage-dependent cation channels. Na+ and K+ ion channels have already been identified and functionally analyzed in Schwann cell cultures.2 Because they share the same specifications as the ion channels of the axon membrane, it was assumed that the myelin sheath supplies the axon with ion channels.3 We will show that in selected former experimental studies, both the excitability and the generation of induced voltages of the Schwann membranes had already been documented—but not recognized as such. A new physical property, which inevitably arises as a consequence of membrane excitability, concerns the Lorentz forces that arise in the concentrically aligned Na+ ion channels during their synchronous depolarization. They generate a mechanical constriction wave that moves across the myelin sheath in the direction of excitation. This mechanical wave has already been documented for unmyelinated axons.4 Thus, the myelin sheaths not only bear the brunt of nerve conduction but also possess a pumping function that enables the rapid – already known – submembranous substrate transport of the axon. On this basis, models of the pathophysiology of Alzheimer’s disease and Parkinson’s disease can be developed, because both diseases obviously show a disturbance of intra-neural substrate transport. Introduction Over the past decades, valuable experimental studies on the anatomy and physiology of myelinated nerves have emerged. The evidence obtained in these studies was interpreted by the authors against the backdrop of a supposedly inactive myelin sheath. The resulting inconsistencies have, to date, prevented these evidences from being compiled into a coherent model. Here, studies with outstanding key evidence will be re-evaluated. Evidence The distribution pattern of Na + and K + ion channels in the axolem of myelinated nerves is excellently documented in the work of M.A. Bhat et al. 5 (Fig. 1). The axon possesses Na + ion channels (right: yellow, left: light blue) only in a narrow circumferential strip in the center of the nodule. The K + ion channels (red) are located exclusively in the inter-nodal axon segment. Fig. 1 Left: The neurexin/contactin/paranodin barrier (NCP, dark blue) separates Nav1 from Kv1 channels (+/+) in axons of the sciatic nerve (SN); Right: (-/-) = “NCP knockout”; dark blue fluorescence disappeared, Kv1 channels (red) touch the zone of Nav1 channels in the nodules (yellow) without mixing. The “comet’s tail” (red, left image) disappeared with the “NCP knockout.” They are formed by the loop channels operated by the Schwann cells. Thus, only the axonal channels remain. 5 There they are arranged in a longitudinal line across the entire internode of the axolem. This line will correspond to the opposite course of the inner mesaxon of the myelin sheath. Perpendicular to this line are individual stripes running circularly around the axon, which will correspond to the location of the Lantermann notches. In the right part (-/-) of Figure 1, only the K + ion channels of the axolem are shown due to the disruption of the neurexin/contactin/paranodin barrier. Their broad cuffs can be seen circulating the axon pre- and post-nodal and touching the narrow strip of Na + ion channels. These K + ion channel fields are normally separated from the Na + ion channel strip of the nodule by the neurexin/contactin/paranodin barrier (blue). The representation in Figure 1 (left) (+/+) shows, in addition to the K + ion channel fields of the axolem, the distribution of K + ion channels in the accessible portion of the Schwann membranes. The peri-axonal space is hermetically sealed by the Schwann cell through tight junctions at all points of contact with the axolem. This space is also an extracellular compartment for the Schwann cell itself. It has no connections to the extracellular spaces of the lamellae. If there were, the marker would also have stained the K + ion channels in the Lantermann notches. The Schwann cell thus operates two hermetically sealed extracellular spaces: the extra-intraspace of the lamellae and the extra-extraspace between the axon and the Schwann cell. The marker has therefore penetrated the extra-extraspace only. There, it has stained the longitudinal K + ion channel stripe on the inner mesaxon lip. The surrounding Schwann membrane cannot contain voltage-dependent K + ion channels at the site of the Lantermann notches because these would be positioned in a mirror image of the K + ion channels of the axolem and would be hyper polarized with the excitation wave—thus remaining closed. The pre- and post-nodal ”comet´s tail” is particularly striking. The K + ion channels stained therein are located in the membranes of the loops (Fig.10), which extend up to the outermost lamella level. It is also noteworthy that no Na + ion channels were detected in the Schwann membrane, which borders the peri-axonal extra-extra space. Based on these results, it is evident that the internodal axolem is not excitable. Voltage-dependent K + ion channels can be depolarized, but then, with the K + ion export, they generate hyperpolarization of the axolem, which prevents self-sustaining excitation propagation. Evidence A study by G. David et al. 6 is very insightful in elucidating the electrophysiological mechanisms of excited myelinated nerve fibers. The stereotypical experimental procedure consists of inserting a cannulated, electrolyte-filled glass probe into the Schwann sheath perpendicular to the axon axis, advancing it into the axon, and then measuring electrical signals via the probe after gradually withdrawing it and repeatedly stimulating the nerve. (Fig. 2) Fig. 2 Voltage measurements using microelectrodes (3 M NaCl and 50 mM KCl). The inserted electrode is gradually withdrawn through the myelin sheath, starting in the axon. At time (a), the electrode tip is in the axon (MRP -80mV). The summation potential recorded in the axon (a) is shown on the left. When the electrode is withdrawn from the axon, the MRP is consistently 0mV when the electrode tip is in the myelin sheath. As the electrode is gradually withdrawn, the amplitudes of the peri-internodal summation potentials steadily decrease (b–f). The bold black lines above the time recording indicate the temporal sequence of the experimental steps. 6 What did G. David measure? At each probe position, the fiber was stimulated, and a consecutive excitation-induced voltage spike was recorded. This voltage spike ostensibly has the shape of an action potential (AP). An AP is always a change in membrane potential over time. In position (a) in Figure 2, the probe tip is inserted into the axon with its cannula opening. The resting membrane potential (MRP) of the axon is measured at approximately -80mV. Together with the stimulus pulse (small pre-spike), the probe then measures a depolarization of the axon that almost reaches the 0mV level. This is also what an AP looks like. However, if it were indeed an AP, then the axolem at the location of the probe tip would have to be depolarized at the moment of excitation. The inter-nodular axolem (Fig. 1) does not have voltage-dependent Na + ion channels—these are found exclusively at the nodule. Thus, no membrane depolarizations can occur in the inter-nodal segment of the axolem. There remains a theoretical possibility that the imported positive charge [Na + ] of the depolarization at the nodulus (membrane strip width 1 µ) is large enough to depolarize the relatively long inter-nodular axolem segment (approximately 1000 µ) along its entire length. However, regardless of the imported positive charge, this is effectively prevented by the wide para-nodal axolem cuff, densely populated with K + ion channels (Fig. 3). There, the membrane depolarization of the nodulus generates an appropriate K + ion export into the peri-axonal extra-extra space of the Schwann cell, which preserves the axolem’s MRP in the immediate vicinity of the nodulus. Thus, axonal excitation always remains limited to the nodal axon segment and its immediate vicinity. At the probe site, the membrane potential of the axolem never changes, so the MRP remains constant at -80 mV. Therefore, the origin of signal (a) in Figure 2 is initially unexplained. Fig.3 Axon membrane pre-nodal (left) and nodal (right). The Neurexin/contactin/paranodin area (bold red) between the K + ion channels and the Na + ion channels separates the two external sides of the membrane into two electrophysically separate capacitor plates. Intracellularly, the capacitor plate (red top line) is continuous. If both channels (K = K + ion channel, Na = Na + ion channel) are opened synchronously, a shunt current (i S ) is created. i Na = Na + ion current, i K = K + ion current. To explain signal (a) in Figure 2, a previously neglected physical quality must be inserted into the general excitation process. It is an inductive voltage signal. This can only be generated by the Na + ion channels of the Schwann membrane during the depolarization process. Evidence Induction voltages in the context of cardiomyocyte excitation have been documented for more than a hundred years. If monophasic potentials are recorded from a cardiac strip preparation, they are superimposed by “remote potentials” as the length of the cardiac strip increases (Fig. 4). This phenomenon was first described in 1914 by Thomas Lewis 6-19 as “extrinsic effects”. With current knowledge, these “extrinsic effects” can be identified as induction voltages. Fig 4: Measurement of splittings (left) and post-fluctuations (right) in monophasic recordings on a frog heart strip; electrode spacing: a = 5 mm, b = 10 mm, c = 20 mm, d = 30 mm, e = 40 mm. Splittings and post-fluctuations increase as the distance between the electrodes increases. The length of the curve complex increases as well. Splittings are located on the plateau of the curve. Post-fluctuations are located on the falling curve branch at the end of the action potential. Calibration = 20 mV. Suction injury. 14,15 The time scaling on the abscissa is (almost) identical in all 5 figures. Today, with a focus on the membrane plane, the depolarized voltage-dependent Na + ion channels can be identified as the generators of inductive magnetic fields. The “overshoot“, known since 1939 also occurs due to induction voltage. 20,21,22 For the myocardium, it is therefore also evident that the cardiac magnetic field, known for decades, 23 also possesses inductive properties. The inductive magnetic field is generated by the collective depolarization of the Na + ion channels. 24 Schwann cells and the axolem also possess functionally similar Na + ion channels. This means that signal (a) in Figure 2 is an inductive-magnetic one. It must have originated in the Schwann sheath. Because inductive-magnetic fields penetrate matter, the induced voltage vector can overlap with the electrolyte column in the glass cannula, thus simulating a depolarization of the axolem. Fig. 5 Electrophysiological circuit diagram showing the probe’s operation. The tip of the glass cannula is in the axon. The MRP in the axon is consistently -80 mV. The square shows an enlarged section of a double membrane. m = membrane, my = myelin. A Na + ion channel (gray rectangle) is located in the ab-axonal membrane. The direction of movement of the Na + ions is indicated by the arrow. During depolarization, the resulting induced voltage vector impedes the flow of Na + ions. The polarity of this vector is indicated by the arrow in projection with the glass cannula. The magnitude of this vector results from the summation of all individual vectors of the lamella levels. The polarity of this summation vector has a depolarizing effect in the axolem. The K + ion channels located in the internodal axolem open and generate hyperpolarization because the Na + ion channels are missing there. Therefore, no action potential can develop. A signal is measured (square right), but it looks like an action potential. The amplitude of this signal (almost 80 mV) corresponds to the magnitude of the induced voltage vector. Because the cannula short-circuits the membrane potentials of the extremely narrow lamellae at its puncture site, thus electrically neutralizing them, a 0mV resting potential is measured there in Figure 2 b-f. Due to the membrane short-circuit, no action potentials can be generated in the lamellar membranes in the immediate vicinity of the perforation site with the passing induction wave. Therefore, the signals b-f must also have been generated by distant induction voltages. The inductive magnetic field of the Schwann membranes created during excitation consists of a summation of the fields of individual lamellae. The magnetic field planes are parallel to the curved membrane planes. In measurement (a) the induction voltage vector of the entire summation field is detected. The further the cannula is withdrawn from the Schwann sheath – from the magnetic field – the shorter the proportional section of the measured induction voltage vector becomes. At this point in the arguments, the evidence for Schwann cell excitability is sufficiently established. It results from evidences 1-3 listed above. Thus, an electrophysiological model of the Schwann sheath can now be developed. The experimental evidence required for this is also sufficient. This model will be briefly outlined here. Electrophysiological Model of the Schwann Sheath The excitations are generated in the extremely narrow lamellar levels by voltage-gated Na + ion channels. These tiers consist of double membranes that alternately enclose an intracellular and extracellular space. (Fig. 5) Every other membrane is myelinated and therefore non-excitable. Furthermore, the electrical membrane capacitance is reduced by the myelin sheath. The question of which of the two membranes is myelinated can be answered by the direction of the Na + ion currents in the excited nodule membrane. Because nodule depolarization generates an induced voltage vector that can depolarize the subsequent Schwann apparatus at the outermost lamella, the active membranes of the nodule and Schwann lamella must be isoelectric to each other. The positions of two membranes are isoelectric if their ion channels have the same orientation. This means that only the ab-axonal membranes are excitable, and the ad-axonal membranes are sealed with myelin. If it were the other way around, the nodular induced voltage vector would have a hyperpolarizing effect in the myelin sheath—thus preventing depolarization. Fig. 5 Cross-section of a sector of a myelinated nerve fiber. The axon is on the left of the image. The myelinated membranes are black. The uniform spacing between the black lines is an electrophysiologically based prerequisite for the functionality of excitation conduction. The depth of the intracellular and extracellular space is 1nm each. Based on these minimum values, the following spatial distribution would result (Fig. 6): (1 myelin membrane 2nm) + (2 spaces = 2nm) + (2 membranes = 10nm) = 14nm If a lamellar unit is 14nm thick, then 14 windings fit into 200nm. This can be seen in Figure 5. Fig. 6 Scale-correct lamella structure of two periods of the myelin sheath, upper edge of the image = central direction, M = cell membrane, ad-axonal and ab-axonal, EX = extracellular space, IN = intracellular space, my = myelin layer. Minimizing the IN and EX spaces requires a precisely calculated ionic load. If (nq) is the number of positive charges (q) that are transmembranely shifted with a membrane depolarization, then the entire ion distribution pattern is based on this quantity. This charge quantity is found in the MRP state as (nNa + ) extracellular. Due to the electrical insulation from the peri-axonal extra-extra space of the Schwann sheath, the contingent (nNa + ) in the hermetically sealed extra-intra space generates a positive electrical potential. Accordingly, the absence of this contingent in the intra-intra space generates a negative potential in MRP. If one roughly assumes that the potential difference between the intra-intra and extra-intra space – i.e. the MRP – in the Lantermann notches and the loops is set to about -80mV by the work of the K + ion channels present there, then the lamellar spaces in the MRP would have the potentials: IN EX -40mV +40mV The tonicities of the spaces separated by unmyelinated membranes must be balanced in the MRP state. If this were not the case, a transmembrane shift of water would occur. If there were only Na + ions in the EX-space and only K + ions in the IN-space, then the tonicity would be greater in the EX-space than in the IN-space at an MRP of (-40 mV/+40 mV). The necessary balance is achieved with Ca ++ ions in the extra-intra space. While maintaining extracellular positivity, Ca ++ ions can reduce the tonicity there due to their bivalence. Cl - ions pose a problem in that they can diffuse relatively freely transmembranely and always take the path to the positive side. They cannot be locked in. Because they are not involved in the excitation process, a hypothesis should be introduced at this point, in accordance with the model: The myelin sheath is largely free of Cl - ions. Ca ++ ions are imported from the axon. 25 This evidence fits well with the need for the myelin sheath to be able to export excess Na + ions into the axon via the internodal axolem. Because the internodal axolem is devoid of Na + ion channels, Na + ion import into the axon can only occur via an exchange with Ca ++ ions (3 Na + IN/1 Ca ++ EX). Na + ions are continuously deposited peri-axonally, 1. because the physical damping of the excitation oscillation leaves behind lost Na + ions in the intra-intra space, which are then shifted further centrally and finally disposed of in the axon. 2. because the supply of K + ions comes from the internodal axon. By means of Na + /K + ATPases, the K + ions are then transported peripherally in the myelin-free Lantermann grooves and loops in exchange for Na + ions, and the Na + ions are transported centrally. The Ca ++ ions accumulate only in the extra-intra spaces. In their patch-clamp experiments on Schwann cell cultures, Chiu et al. conducted a series in which stimulation was also carried out stepwise with positive membrane voltages. Fig.3c illustrates a family of ionic currents which includes depolarization sufficiently strong to elicit outward transient currents . The pipette solution contained primarily CsCl to block current through K + channels but included 29mM Na + . We consistently found that the apperent reversal potential was about +70mV , which is about 30mV more positive than the Na + equilibrium potential. 2,3 What should the ion distribution pattern and the MRP in the lamellae then look like? If (nNa + ) is the contingent that passes from the EX-space to the IN-space with depolarization, then the following pattern arises in the MRP: IN EX -35mV +35mV 2 (nK + ) 1 (nNa + ) + 1 (nCa ++ ) The tonicity of both sides is identical. The electrostatic ratio is 2:3. When (1/2 nNa + ) switches from EX to IN, the electrostatic ratio is equalized (2.5:2.5), and the MP = 0mV. If another contingent (1/2 nNa + ) follows, an overshoot of +35mV occurs, and the MP is reversed. IN EX +35mV -35mV 2 (nK + ) + 1 (nNa + ) 1 (nCa ++ ) The tonicity of both sides then has a ratio of 3:1. The electrostatic IN/EX ratio at the end of the depolarization is 3:2, which is the opposite of the ratio before the depolarization. This means that after the depolarization, the same voltage gradients are at work as before the depolarization—but in reverse directions. Now, the same voltage-dependent Na + ion channel used for the depolarization will reopen for repolarization when the +70mV mark is reached. (Table 1) IN EX MRP -35mV +35mV ΔU =-70mV ΔU = -35mV 0mV 0mV U ind = -35mV Depo +35mV -35mV ΔU =+70mV ΔU = +35mV 0mV 0mV U ind = -35mV MRP -35mV +35mV ΔU=-70mV Σ280mV Table 1: Measurement protocol of a Schwann membrane excitation cycle. The sequence proceeds from top to bottom. The oscillation consists of a depolarization followed immediately by a repolarization. The membrane potential ranges from 2 x 140mV = 280mV. The induced voltage (U ind ) built up in the first half of depolarization or repolarization enables the continuation of the Na + ion currents in the second phase, generating an ”overshoot.” For this to happen, the induced voltage must have a hyperpolarizing effect. By convention, (U ind ) is given a negative sign. The membrane potentials (ΔU) in the first phase each have a direction and, by convention, have opposite signs. The Na + ion channels of the Schwann cell thus enable an otherwise unusual Na + ion-assisted repolarization, because K + ion channels are not present in the lamellae. Since a similar constellation exists in the nodulus membrane, it can be assumed that the same Na + ion channels also enable both depolarization and repolarization at the nodulus. An ”overshoot” essentially corresponds to a positive charge that is transported through the Na + ion channels in addition to compensating the electrical membrane capacitance. For this to be possible, the density of Na + ion channels must be greater than that required to compensate the electrical membrane capacitance only. Therefore, the density of Na + ion channels in the myocardial membranes and the nodulus is particularly high. Both generate a large ”overshoot,” which corresponds to a high induced voltage, which in turn opens the still-closed Na + ion channels in the surrounding area. In the Schwann membrane excitation process, half of the MP reached is an ”overshoot.” Thus, the excitation process takes the form of a symmetric biphasic oscillation. (Fig. 7) Fig. 7 Schematic representation of de- and repolarization of the Schwann membrane as an oscillatory process. The left half of the diagram symbolizes a membrane capacitor with its two EX-IN plates. In the right half of the image, the same capacitor is shown mirrored with its IN-EX plates. At -70 mV (bottom left, dark blue graph), the synchronous collective Na + ion movement (1 ion per channel) of all channels in a membrane area begins. An ion collective is moved that corresponds to the total capacitor charge, including the overshoot of +35 mV per active membrane area. As this Na + ion collective (left light blue vertical bar) moves towards IN, this collective essentially represents a capacitor plate moving towards the opposite side. Because the electric field decreases proportionally to the reduction in the plate distance, the capacitor voltage (green) decreases linearly and reaches zero when the IN plate is reached. Synchronously with this process, the charge of the ”overshoot” (50% of the total charge) builds up a counter-field (red) retrograde to the EX-plate, which increases proportionally with increasing distance between the EX-plate (left) and the location (d) of the ion movement (light blue bar). The green and red hatched areas symbolize the magnitude of the oppositely polarized electric fields based on the height of the line stacks at the location of the ions (light blue bar). The dark blue graph results from the difference between the opposing electric fields at location (d). It denotes the effective differential voltage that accelerates the ions. In the center between the plates, the dark blue graph passes through the 0mV mark. There, the acceleration is zero. Without the already increased magnetic induction, the capacitor charging and discharging would come to a standstill. The diagram in the right half of the image shows the process of repolarization. It is mirror-symmetrical to the depolarization. Finally, according to the Cl - ion hypothesis, a clinically relevant property of the myelin sheath will be discussed. This involves the exclusion of Cl - ions and the associated hypertonicity in the central lamellar layers. Both properties carry the risk of overhydration. A well-studied example is the hypertonic endolymph of the inner ear. (Fig.8) An interruption of the oxygen supply causes the hypertonicity to collapse within just 10 minutes. The rapid uptake of water and Cl - ions by the endolymph deafens the inner ear – sudden hearing loss. Fig. 8: Graph of the positive endolymph potential (EP) over time after the oxygen supply is interrupted. With the ingress of Cl - ions, it drops to -40 mV. (From: Cochlear Fluids Lab, Washington University) A similar overhydration of the Schwann cell or oligodendrocyte in the presence of oxygen deficiency would ultimately lead to irreversible rupture of the myelin sheath. In the oligodendrocytes – the white matter – this process would result in the clinical picture of cerebral edema. The risk of cerebral edema is well known at high altitudes. The following considerations should be made regarding the hypothesis of hypertension in the central lamellae of Schwann cells and oligodendrocytes: 1. The excitation-triggered ion exchange of K + and Na + ions in the levels of Lantermann notches and loops, with identical contingents in all levels, should logically lead to an enrichment of K + and Na + ions in the central levels, because the spaces become smaller centrally for geometric reasons. 2. Such an enrichment would allow an increase in the density of Na + ion channels in the central membranes, thus generating a depolarization with a stronger induction at a higher MRP. This increase would increase the radius of synchronous depolarizations and thus increase the signal velocity. 3. At the same time, a reduction in the density of Na + ion channels in the peripheral levels would weaken the induction generation there and thus impair the environment of the nerve fiber less inductively. 4. In the peripheral levels, signal transmission occurs from the nodule to the Schwann sheath. A low MRP is helpful because it shortens the distance to the membrane threshold, thus increasing transmission reliability. The high pressure-sensitivity of myelinated nerve fibers (ulnar nerve!) could be an indication of this property. The membrane is a capacitor. If the plate spacing is reduced by pressure on the membrane—i.e., the membrane is stretched—the membrane voltage decreases proportionally to the plate spacing. If the membrane threshold is reached, the Na + ion channels spontaneously depolarize due to pressure and trigger an excitation wave. 5. Because the minimum MRP is set at -70 mV, this value should not be exceeded, because then repolarization would fail and the Na + ions would remain in the intra-intra space. If this happens, however, the induced voltage of the summation magnetic field of the entire myelin sheath would compensate for this deficiency. The experimental results of David et al. (Fig. 2) provide an answer to the question of whether the magnetic induction field of the myelin sheath is homogeneous during excitation. The probe is inserted in position (a) with its tip in the axon. Triggering an excitation generates an induction voltage of almost 80mV. This induction signal is physically identical to signals (b-f) – except that the latter begin at a different voltage level (0mV). If all voltage signals are set to the same initial level, the arrangement shown in Figure 9 is obtained. The sequence of measurements was obtained by gradually withdrawing the probe from the myelin sheath. Even though no distance data are available for the individual steps, the overall result clearly shows an inhomogeneous induction field. Significantly larger induction voltages are generated in the innermost lamellae than in the peripheral ones. If it were otherwise, the reduction of the induction voltages would have to occur linearly across the width of the myelin sheath, which is not the case in Figure 9. Fig. 9: Sketch of the measurement results as in Figure 2. Only the a-wave was set to the same voltage level as the waves (b-f). This distribution pattern generates a higher conduction velocity in the central lamellae than in the peripheral ones. This also means that although the peripheral lamellae are initially depolarized by the nodulus signal, the induction field of the central membranes then takes over as the excitation progresses. The central lamellae end well before the end of the myelin sheath. Ultimately, it is again the outer lamellae that transmit the excitation to the next nodule, presumably with the assistance of the central induction signal. (Fig. 10) Fig. 10 Longitudinal section of a myelinated nerve fiber near the nodulus. The nodulus membrane is on the right, the axon with its microtubules and filaments is below. The myelinated lamellae terminate in staggered loops, all of which extend to the axolem. The loops of the peripheral layers extend close to the nodulus. Conclusion The dogma of the inexcitable myelin sheath lacks evidence. It is all the more incomprehensible that it remains unchallenged to this day. The consequences of this error are devastating for neuroscience. In particular, the lack of knowledge of the mechanical activities of the myelin sheath prevents understanding of the undeniably present intraneuronal substrate circulation. This is evident in the striking images of MRI tractography of the brain. Because neuronal cell death in Parkinson’s and Alzheimer’s disease is evidently caused by pathological TAU, which disrupts microtubular substrate transport, the mechanics of the intraneuronal substrate circulation should actually be the focus of research. But this is prevented by the dogma. Acknowledgements The author thanks the Private Institute for Theoretical Electrophysiology for support. Competing interests The author declares: no competing interests. References 1. David G, Barrett JN, Barrett EF. Evidence that action potentials activate an internodal potassium conductance in lizard myelinated axons. J Physiol 445:277-301 (1992) 2. Chiu SY, Schrager P, Ritchie JM. Neuronal-type Na + and K + channels in rabbit cultured Schwann cells. Nature Vol. 311, 156-157, 1984 3. Schrager P, Chiu SY, Ritchie JM. Voltage-dependent sodium and potassium channels in mammalian cultured Schwann cells. Proc. Natl. Acad.Sci. USA, Vol. 82, 948-952, 1985 4. Heimburg, T. Mechanical aspects of membrane thermodynamics. Estimation of the mechanical properties of lipid membranes close to the chain melting transition from calorimetry (1998) Biochim. Biophys. Acta 1415, 147–162, 1998 5. Bhat MA, Rios JC, Lu Y, Garcia-Fresco GP, Ching W, Martin MS, Li j, Einheber S, Chesler M, Rosenbluth j, Salzer JL, Bellen HJ. Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/caspr/paranodin. Neuron 30:369-383 (2001) 6. Lewis, Th. Der Mechanismus der Herzaktion und seine klinische Pathologie. Wien und Leipzig (1912) 7. Lewis, Th., J. Meakins & P. B. White P. B. Philos. Trans. roy. Soc. Lond., Ser. B 205 , 375 (1914). 8. Drury, A. N. & Brow, G. R. Heart 12, 321 (1926). 9. Gilson, A. S. Amer. J. Physiol. 82, 531 (1927). 10. Woronzow, D. S. Pflügers Arch. 160, 581 (1915). 11. Woronzow, D. S. Z. Biol. 86, 231 (1927). 12. Schütz, E. Einphasische Aktionsströme, Säugetierherz. Z. Biol. 92, 441 (1932) 13. Rothschuh, K. E. Fernpotentiale bei örtlicher Aktionsstromableitung. Verh. dtsch. Ges. Kreislaufforsch. 1941, 299. (1941) 14. Rothschuh, K. E. Über den Anteil von Fernpotentialen am Aktionsstrombild des Herzens bei örtlicher Ableitung. Zeitschrift für die gesamte experimentelle Medizin (Z. exper. Med. Springer) Volume 110, pages 154–174, (1942) 15. Mehring, C. E. Elektrisches Aktionsphänomen. Z. Biol. 100, 68 (1940) 16. Lerche, E. Verh. dtsch. Ges. Kreislaufforsch., 13. Tagg 1940, 171. (1940) 17. Schaefer, H. & Trautwein, W. Pflügers Arch. 253, 152. (1951) 18. Schütz, E. Physiologie des Herzens. Springer Verlag, Berlin, Göttingen, Heidelberg Germany Seite 70 (1958) 19. Weidmann, S. Elektrophysiologie der Herzmuskelfaser. Bern und Stuttgart, Germany (1956) 20. Cole, K. S. & Curtis, H. J. Electric Impedance of the Squid Giant Axon during Activity. Physiol. 22, 649 (1939) 21. Hodgkin, A. L. The relation between conduction velocity and the electrical resistance outside a nerve fibre. J. Physiol. 94, 560. (1939) 22. Pumphrey, R. J., Schmitt, O. H. & Young, J. Z. Correlation of local excitability with local physiological response in the giant axon of the squid (loligo). J. Physiol. 98. 47. (1940) 23. Brisinda, D., Fenici, P. & Fenici, R. Clinical magnetocardiography: the unshielded bet – past, present, and future. Front. Cardiovasc. Med. 10:1232882 (2023) 24. Herzberg, W. Evidence for inductive magnetic fields of the heart. 2025 EHJ, pending 25. Zhang, Chuan-Li, J. Adam Wilson, Justin Williams, and Shing Yan Chiu. Action potentials induce uniform calcium influx in mammalian myelinated optic nerves. J Neurophysiol 96: 695–709, 2006; Supplementary Material File (image1.emf) Download 464.52 KB File (image2.emf) Download 825.69 KB Information & Authors Information Version history V1 Version 1 29 August 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords electrophysiology excitability ion-channels oligodendrocyte schwann cells Authors Affiliations Wolfgang Herzberg 0009-0002-8056-3980 [email protected] University of Applied Sciences Wedel View all articles by this author Metrics & Citations Metrics Article Usage 178 views 106 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Wolfgang Herzberg. Evidence for excitability of Schwann cells. Authorea . 29 August 2025. DOI: https://doi.org/10.22541/au.175647904.43087524/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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