Myelin sheaths can act as compact temporary oxygen storage units as modeled by an electrical RC circuit model

Abstract Oxygen is a crucial component in cellular energy metabolism, particularly in the brain where neurons consume the majority of energy produced via mitochondrial oxidative phosphorylation. Phospholipid membranes have been found to store and transport oxygen efficiently in their hydrophobic core. This work investigates the kinetics of this storage, not only in a single membrane but also in membrane stacks as those found in myelinated axons in the nervous system. Using a diffusive model derived from molecular dynamics simulations, it is first demonstrate that oxygen storage within a phospholipid bilayer follows first-order kinetics. In consequence, we show how oxygen loading and unloading in a membrane is effectively modeled by an intuitive RC (resistor-capacitor) circuit analogy with a characteristic RC time constant. Next, oxygen transport through myelin, comprising multiple bilayers, could be investigated by building a ladder network of RC circuits. Both the resistance (to oxygen transport) and the capacitance (for oxygen storage) scale linearly with the number of bilayers. Moreover, the characteristic time constant for oxygen storage scales quadratically with the myelin thickness, for instance enhancing the characteristic time constant from 30 ns for one 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer to 506 μs for 200 POPC bilayers. This enhancement gives myelin a buffering role: myelin sheaths act as spatially compact oxygen containers whose slower kinetics will dampen sudden oxygen changes. Finally, oxygen transport from capillary to axonal mitochondria is modeled during increased oxygen consumption rates (OCRs) associated with neuronal activity. The model predicts that increased myelination results in longer sustainment of increased oxygen demand, supporting the idea that myelin sheaths may act as a buffer to oxygen fluctuations. The inability of considered configurations to sustain the increased OCRs for periods longer than a few hundred milliseconds hints the functional aspect of the dominant vascular response in restoring oxygen homeostasis following neuronal activation.