title: The proton pump/leak mechanism of unconsciousness.
abstract: There are few explanations which account for the manner in which the catastrophic physiological consequences of anaesthesia, cold narcosis or, for the matter, a short, sharp upper-cut, come about. Most studies terminate with the presentation of ever-better correlations between an end-point in a model system (dough consistency, rubber elasticity, bacterial, protozoal or animal mobility, liposome permeability, luciferase activity, etc.) and oil/water partition coefficients or with some arbitrary biological end-point. From what is currently known about the permeating pathways of non-electrolytes, ions and protons across membranes e.g. liposomes, the effect of anaesthetics on such pathways and the effect of temperature and pressure on both liposomes and whole animals, it is possible to develop a testable hypothesis. It is called the 'proton pump-leak' hypothesis and involves a number of linked biophysical and biochemical processes. It assumes that a living animal or plant is in a steady-state regarding all concentration gradients; passive leaks across membranes are balanced by temperature, pressure, and energy dependent ion/ion and/or proton/ion pumps (enzyme), working within an aqueous phase. Consciousness is dependent upon inter-neuronal communication via release of transmitter substances. Transmitter substances, characteristically either weak bases or weak acids e.g. catecholamines, accumulate passively in vesicles rich in acid-buffer, held to a low pH by the activity of H+/K+ energy-driven pumps. Interference with this finely-balanced system either by changing the chemical potential of the hydrophobic (membrane) phase at NTP (with anaesthetics), or by changing the chemical potential of both hydrophobic and aqueous (pump) phases by hyperbaric, hypothermic, or anoxic conditions imposed (inevitably) on the whole animal, would result in the resetting of the steady-state parameters.
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D006801:Humans; D008081:Liposomes; D008959:Models, Neurological; D010539:Permeability; D011522:Protons; D009435:Synaptic Transmission; D013816:Thermodynamics; D014474:Unconsciousness
chemical_list: D008081:Liposomes; D011522:Protons