I co-authored some papers with Morelli and Panfoli, and I agree with their hypothesis that myelin may feed ATP to axons (Adriano et al, 2011; Ravera et al, 2016). However, such ATP-feeding activity, if really existing, is probably not finalized to increasing conduction speed. The latter is not dependent on ATP. It rather depends on opening rate of voltage-gated sodium channels, and on their distance from each other. ATP intervenes only after action potential, by fueling Na/K ATPase that restores membrane polarization. Thus, the ATP-feeding role of myelin to axon may not explain conduction speed, it can rather explain the trophic role of myelin towards axon. The latter role is evident for example in the axonal degeneration that follows demyelination in multiple sclerosis, degeneration that is currently still largely unexplained and could, by contrast, be nicely explained by an ATP-feeding role of myelin towards axons.
The observation of Maurizio Balestrino helps us to cite some literature data that we did not mention in our preprint. The accurate measurements of J. M. Ritchie & RW Straub (1980-PMID: 7441528) are fundamental (but there are other reports with similar measures performed) and show a consumption of oxygen and ATP after non-myelined nerve stimulation. I agree that the conduction speed depends on the speed at which the Na and K voltage gate channels operate, but this operativity is allowed if the distribution of ions is correct and must be done before stimulation pass. If the external Na and internal K ion concentrations are not restored to the right value, the voltage gated pumps can not operate and operate only if the sodium / potassium pump has just carried out its ATP consuming work, ie if the cytoplasm has been filled with ATP, that, according to our hypothesis, in myelinated nerves is supplied by myelin. On the other hand, the recent Trevisiol et al. paper (2017 PMID: 28414271) ascertains that firing in myelined nerve decreases the ATP of the system nerve+ myelin sheath. This elegant experiment shows a direct link between firing in myelined nerve and ATP supply and it is also shown the reverse, ie that if the system is blocked in oxidative phosphorylation by azide (that is, if no ATP is produced) the conduction velocity slows down dramatically.
The work from prof. Morelli and his colleagues gives us a new perspective in neuronal physiology and makes a lot of sense. However, the scientific society is not very fond of this idea, but do not give any precise counter arguments.
I hope this project unveils a new perspective in pathophysiology of neurodegeneration and demyelinization of CNS neurons (for example in MS).
Only today I learned of a research developed in 1991 (Lindström & Brismar, 1991, Mechanism of anoxic conduction block in mammalian nerve. Acta physiologica Scandinavica 141:429–33) which is compatible with our hypothesis. In fact, Lindström & Brismar observed in a sciatic rat nerve, which is myelined, a drop of around 50% of CAP when this nerve was immersed in Ringer's solution anoxic or containing dinitrophenol. The authors conclude that such treatments lead to the “inhibition of another ATP- dependent process in the axon”. Such another ATP-dependent process can be identified in aerobic synthesis and ATP transfer to the axon via gap-junctions, a process that occurs in myelin and was discovered by us in 2009. However, these processes need to be evaluated especially in quantitative-stoichiometric terms, reminding us that energy is not created and not destroyed and that the brain has a high consumption of both glucose and oxygen and is known to be the site of active combustion with production of gaseous CO2 which must be immediately converted into bicarbonate by the carbonic anhydrase enzyme. Gas bubbles is not allowed in the brain. Resounding that oligodendrocytes and myelin are the richest component of this enzyme (Wendy Cammer, 1984, “Biology and Chemistry of the Carbonic Anhydrases” Ann. New York Acad Sci, 429: 494–497). This is the index of active operative combustion in myelin with a plausible energy conversion leading to ATP regeneration. The latter, in the light of our rigorous experimentation documented by numerous papers, passes to the axon to energetically support the conduction of the nervous impulse.
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