Anesthesia & Consciousness
Anesthesiology, 2006, 105, pp. 400-12
The article starts by pointing out that the precise mechanism by which anesthesia works is unclear, simply because the precise nature o consciousness is also unknown. Anesthesia is seen as being driven by London forces, the weakest form of van der Waals force, acting in hydrophobic pockets in protein. In this respect anesthetic gases are seen to differ from other drugs, because their action is at the quantum level, while other drugs act at the chemical level.
Studies have shown the binding of anesthetic molecules can be enhanced near to hydrophobic sites. In particular, Franks and Lieb in the 1980s demonstrated anesthetic action in hydrophobic pockets, and the preponderance of evidence points to most of the anesthetic action being in such regions. Only 15% of proteins have hydrophobic pockets large enough for anesthetic molecules. This may account for why many brain functions such as autonomic drives and evoked potentials are not closed down by anesthetics.
The van der Waal forces involved in the action of anesthetics depends on dipole couplings between atoms or molecules. There are three versions of these forces involving attraction between permanent dipoles, attraction between a permanent dipole and electrons capable of being polarised, and the third type known as the London force, which acts between two normally neutral but polarisable atoms or molecules, with temporary dipoles being created. London forces are sensitive to the distance between electron clouds, and the forces are very weak, but acting collectively they can become strong enough to control the conformation of protein.
Proteins perform their functions in the body and brain by changing shape and conformation, involving switching between energy minima. Proteins are linear chains of amino-acids, which fold into three dimensional conformations driven by hydrophobic amino acid-groups. Some of these form hydrophobic pockets in which London forces are able to influence the conformation of the protein. Anesthetics are known to bind not only in the membrane, but also in a number of locations within the neuron, including the tubulin of microtubules.
During the 1960s and 1970s the biophysicist, Herbert Fröhlich, proposed that fluctuating dipoles in proteins in the cell membrane or cytoskeleton would synchronously couple, and being pumped by metabolic energy, the proteins would oscillate in a pumped Bose-Einstein condensate. Hameroff mentions some more recent evidence supportive of some form of biological oscillation.
Anesthesia produces immobility, amnesia and loss of conscious awareness. Research in recent years has suggested possible sites for all three of these functions, with the spine as a favoured site for immobility, the dorsolateral prefrontal for amnesia, and thalamocortical and intracortical networks for consciousness.
A study by John and Prichep showed that loss of consciousness under anesthesia occurred over only 20 ms and involved interruption of the gamma synchrony between the frontal and posterior cortex. Hameroff regards the gamma synchrony as the best established neural correlate of consciousness (NCC). Experiments have shown that the gamma synchrony involves synchronised voltage fluctuations in various regions of the cortex and thalamus. The gamma synchrony is related to dendrite-to-dendrite gap junctions, influences by the dendrite cytoskeleton, rather than axonal synapses. Studies have shown that anesthetics effect dendrites and gamma synchrony more than axons and neurotransmitter release. Hameroff speculates that precise synchrony requires some form of quantum field, since normal brain signalling, even via gap junctions, involves delay. Gamma synchrony is also seen as a candidate to enable the binding process, by which the varied contents of consciousness are conceived as a unity. The gamma synchrony is related to dendrite-to-dendrite gap junctions, influences by the dendrite cytoskeleton, rather than axonal synapses. Studies have shown that anesthetics effect dendrites and gamma synchrony more than axons and neurotransmitter release.