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2015 ; 4
(ä): 485
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A pressure-reversible cellular mechanism of general anesthetics capable of
altering a possible mechanism for consciousness
#MMPMID26380161
Vadakkan KI
Springerplus
2015[]; 4
(ä): 485
PMID26380161
show ga
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.