title: A pressure-reversible cellular mechanism of general anesthetics capable of altering a possible mechanism for consciousness.
abstract: Different anesthetics are known to modulate different types of membrane-bound receptors. Their common mechanism of action is expected to alter the mechanism for consciousness. Consciousness is hypothesized as the integral of all the units of internal sensations induced by reactivation of inter-postsynaptic membrane functional LINKs during mechanisms that lead to oscillating potentials. The thermodynamics of the spontaneous lateral curvature of lipid membranes induced by lipophilic anesthetics can lead to the formation of non-specific inter-postsynaptic membrane functional LINKs by different mechanisms. These include direct membrane contact by excluding the inter-membrane hydrophilic region and readily reversible partial membrane hemifusion. The constant reorganization of the lipid membranes at the lateral edges of the postsynaptic terminals (dendritic spines) resulting from AMPA receptor-subunit vesicle exocytosis and endocytosis can favor the effect of anesthetic molecules on lipid membranes at this location. Induction of a large number of non-specific LINKs can alter the conformation of the integral of the units of internal sensations that maintain consciousness. Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines. Externally applied pressure can transduce from the middle ear through the perilymph, cerebrospinal fluid, and the recently discovered glymphatic pathway to the extracellular matrix space, and finally to the paravenular space. The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia. Changes in membrane composition and the conversion of membrane hemifusion to fusion due to defects in the checkpoint mechanisms can lead to cytoplasmic content mixing between neurons and cause neurodegenerative changes. The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics.
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Room A4-08, Toronto, ON M4N 3M5 Canada.
authors.forename: Kunjumon I
authors.initials: KI
authors.lastname: Vadakkan
keywords: Complete hemifusion; Consciousness; General anesthetics; Inter-membrane contact; Membrane fusion; Membrane hemifusion; Neurodegeneration; Partial hemifusion; Pressure reversal; Semblance hypothesis