Hydroxide ions amplified by water entanglement underly the mechanism of general anesthesia

It is believed that inhaled anesthetics occupy hydrophobic pockets within target proteins, but how inhaled anesthetics with diverse shapes and sizes fit into highly structurally selective pockets is unknown. For hydroxide ions are hydrophobic, we determined whether hydroxide ions could bridge inhaled anesthetics and protein pockets. We found that small additional load of cerebral hydroxide ions decreases anesthetic potency. Multiple-water entanglement network, derived from Ising model, has a great ability to amplify ultralow changes in the cerebral hydroxide ion concentration, and consequently, amplified hydroxide ions account for neural excitability. Molecular dynamics simulations showed that inhaled anesthetics produce anesthesia by attenuating the formation of multiple-water entanglement network. This work suggests amplified hydroxide ions underlying a unified mechanism for the anesthetic action of inhaled anesthetics.