ULTIMATE COMPUTING - Quantum Consciousness Studies

Anesthesia: Another Side of Consciousness 155
results in photon emission. The light emission from the luciferase/luciferin
complex is exquisitely sensitive to anesthetic gases in proportion to their
anesthetic potency. Studying the light emission from firefly luciferase, Ueda
(Ueda, 1965; Ueda and Karmaya, 1973) proposed that anesthetic binding at a
hydrophobic site in the luciferase protein induced an inactive conformational state
which prevented the ATP activated excited state which would normally result in
luminescence. In more recent anesthetic studies on firefly luminescence, Franks
and Lieb (1984) corroborated earlier work that anesthetic potency correlated with
luciferase inhibition potency, much like the earlier correlations with solubility in
“lipid-like” hydrophobic environments. They also reported that anesthetic binding
did not cause a luciferase conformational change, and that the anesthetic effects
occurred by competitive binding with luciferin for a hydrophobic site in
luciferase. Franks and Lieb suggested that anesthesia occurs due to displacement
of endogenous ligands from brain neural protein hydrophobic pockets which bear
some resemblance to the luciferin site within firefly luciferase. Displacement of
endogenous ligands would not explain, however, anesthetic inhibition of
functional protein conformational changes which occur in response to stimuli
other than hydrophobic ligands (i.e. voltage change, calcium, other ions).
Ultimately, anesthesia results from impairment of protein conformational
dynamics. As described in Chapter 6, mechanisms which regulate protein states
are not totally understood, but collective, cooperative mechanisms appear
important. The conformational regulation of anesthetic sensitive neural proteins is
schematically summarized in Figure 7.5. Under normal, non-anesthetic
conditions, there is a class of neural proteins which undergoes functional
conformational change in response to appropriate stimuli. These proteins may be
membrane bound ion channels which become permeable to sodium, potassium,
chloride, or calcium ions; membrane bound receptors for acetylcholine, gammaamino
butyric acid (GABA), glycine, aspartate, glutamate or other
neurotransmitters which are coupled to ionic channels; cytoskeletal proteins
which perform a wide range of dynamic intracellular functions; or various
enzymes. Stimuli which induce functional conformational change in these
proteins are thought to include binding of ligands (i.e. neurotransmitters), changes
in voltage, or ionic flux (i.e. calcium ions). These functional conformational
changes may either facilitate neuronal excitatory activity or have inhibitory
effects. The common anesthetic sensitive link for both excitatory and inhibitory
effects appears to be a protein conformational change.
The coupling of conformational states to appropriate stimuli is not clearly
understood; possible explanations were discussed in Chapter 6 and appear to
involve collective, nonlinear coupling of electronic mobility to mechanical
movements. Conformationally coupled electron mobility within neural protein
hydrophobic pockets may thus be essential to highest cognitive function and
sensitive to the effects of anesthetic molecules. Evidence from gas
chromatography (McNair and Bonelli, 1969) and corona discharge experiments
(Hameroff and Watt, 1983) suggest that anesthetic gases can directly alter
electron energy, capturing, retarding, or enhancing their mobility by Van der
Waals-London forces (instantaneous dipole coupling). Thus regulation of protein
conformational state, as proposed by Fröhlich’s theory of coherence, electret
behavior or Davydov’s soliton model, would be directly inhibited by anesthetic
occupancy of protein hydrophobic pockets because the environmental medium for
electron mobility would be significantly altered. Hydrophobic pockets vary in size
and shape among different proteins which would account for the variability
among different anesthetic gas molecules. The weak, reversible Van der Waals
interactions by which anesthetics bind within hydrophobic regions explain the