A scenario for the origin of life: Volume regulation by bacteriorhodopsin required extremely voltage sensitive Na‐channels and very selective K‐channels

<jats:title>Abstract</jats:title><jats:p>The osmotic activity produced by internal, non‐permeable, anionic nucleic acids and metabolites causes a persistent and life‐threatening cell swelling, or cellular edema, produced by the Gibbs‐Donnan effect. This evolutionary‐critical osmotic challenge must have been resolved by LUCA or its ancestors, but we lack a cell‐physiology look into the biophysical constraints to the solutions. Like mycoplasma, early cells conceivably preserved their volume with Cl<jats:sup>−</jats:sup>, Na<jats:sup>+</jats:sup>, and K<jats:sup>+</jats:sup>‐channels, Na<jats:sup>+</jats:sup>/H<jats:sup>+</jats:sup>‐exchangers, and a light‐dependent bacteriorhodopsin‐like H<jats:sup>+</jats:sup>‐pump. Here, I simulated protocells having these ionic‐permeabilities and inhabiting an oceanic pond before the <jats:italic>Great‐Oxygenation‐Event</jats:italic>. Protocells showed better volume control and stable resting potentials at lower external pH and higher temperatures, favoring a certain type of extremophile life. Prevention of Na<jats:sup>+</jats:sup>‐influx at night, with low bacteriorhodopsin activity, required deep shutdown of highly voltage‐sensitive Na<jats:sup>+</jats:sup>‐channels and extremely selective K<jats:sup>+</jats:sup>‐channels, two conserved features essential for modern neuronal encoding. The Gibbs‐Donnan effect universality implies that extraterrestrial cells, if they exist, may reveal similar volume‐controlling mechanisms.</jats:p>