How toxic levels cause rapid loss-of-consciousness (LOC) on a molecular level is poorly understood. Hydrogen sulfide (H2S) is considered a serious industrial safety hazard. A predominantly unitary-type model of volatile anesthetic action is exhibiting effects that appear to result from a multi-site-multi-mechanism model. VA effects are shown to arise largely from "out-of-control" muscarinic and other Gq/11-coupled receptor systems.
The culmination of these, and many other investigations, is a mechanism for VA to target Gq-coupled receptor systems and disrupt downstream systems, receptors and channels. Duncan and Liebman (33) presented a mechanism for VA to interfere with the Stefanov-Tulub reaction and thus affect MT dynamics. Stefanov and Tulub (34) found a spontaneous hydrogen atom transfer reaction in αβ-Tubulin. Researchers such as Rasenick (26,39,92,93,117) have explored the interplay of microtubule (MT) dynamics with Gq-Coupled Receptor components. Minami and Uezono (94,95) have proposed that VA target Gq-coupled receptors. PLC-β activation causes increased, increased PKC activation and PIP2 depletion-all of which affect downstream targets. Volatile anesthetic (VA) inhibition of VGCCs, Na2 + channels and potentiation of extrasynaptic GABAA receptor channels is shown to result from disruption of Gq-coupled muscarinic receptor systems, specifically with the PLC-β signaling pathway.
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