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Fig. 5 | SpringerPlus

Fig. 5

From: A pressure-reversible cellular mechanism of general anesthetics capable of altering a possible mechanism for consciousness

Fig. 5

Formation of different types of reversible inter-postsynaptic functional LINKs. a Two abutted synapses AB and CD. Presynaptic terminals A and C are shown with synaptic vesicles (in blue color). Action potential arrives at presynaptic terminal A releasing a volley of neurotransmitters from many synaptic vesicles inducing an excitatory postsynaptic potential (EPSP) at postsynaptic terminal B. The waveform represents the direction towards which the EPSP propagates. From the presynaptic terminal C, one vesicle is shown to release its contents to the synaptic cleft. This quantal release is a continuous process (even during rest) providing very small potentials to postsynaptic membrane D. Postsynaptic terminals B and D have membrane-bound vesicles marked V inside them. These vesicles contain glutamate receptor subtype 1 (GluA1). Activity arriving at the synapse can lead to exocytosis of GluA1 receptor-subunits and expansion of the postsynaptic membrane. During exocytosis, the vesicle membrane is added to the postsynaptic membrane at locations of exocytosis making this region of the membrane highly re-organisable. This matches with the location where α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunits were shown to concentrate at the extra-synaptic locations extending at least 25 nm beyond the synaptic specialization (Jacob and Weinberg 2014). Note the presence of a hydrophilic region separating postsynaptic terminals B and D. When action potential arrives at the presynaptic terminal, it activates synapse AB and an EPSP is induced at postsynaptic terminal B. The hydrophilic region prevents any type of interaction between postsynapses B and D. Very high energy is required for excluding the inter-postsynaptic hydrophilic region (Martens and McMahon 2008). b Diagram showing the effect of lipophilic anesthetic molecule on the membranes. Incorporation of the hydrophobic anesthetic molecule to the lipid membrane especially at the re-organisable areas that lead to membrane expansion at these locations can provide sufficient energy to exclude the inter-postsynaptic hydrophilic region allowing close contact between the postsynaptic membranes at this region. Action potential arriving at synapse AB reactivates the inter-postsynaptic functional LINK formed by close inter-postsynaptic contact and spreads to postsynaptic terminal D. an membrane segment marked in Turkish blue shows area where membrane reorganization occurs and anesthetic molecules lead to membrane expansion. Formation of large number of non-specific inter-postsynaptic functional LINKs disturbs the net C-semblance formation explained in Fig. 4 leading to loss of consciousness. When the anesthetic molecule is removed, the process reverses back. c Diagram showing formation of a partial inter-postsynaptic membrane hemifusion following anesthesia. Note the interaction between the outer layers of membranes of the postsynaptic terminals. Depending on the lipid membrane composition and the type and concentration of anesthetics, the process of close contact between the membranes described in above section (b) can get converted to a partial hemifusion state. The process can even advance to a reversible complete hemifusion state as described in Fig. 8b depending on several factors. When the anesthetic molecule is removed, the hemifusion reverses back

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