ULTIMATE COMPUTING - Quantum Consciousness Studies

154 Anesthesia: Another Side of Consciousness
effect. However, many other brain regions are inhibited by anesthetics at
concentrations relevant to anesthesia. Further, different anesthetics which have
the same end result have dominant actions at differing areas of the brain, and have
differing characteristics and side effects.
The mechanism of anesthesia, the “other side” of consciousness, is a
beguiling enigma. Efforts to understand the actions of anesthetics began in midnineteenth
century; Claude Bernard observed that the anesthetic chloroform
inhibited “protoplasmic streaming” in slime mold. Around the turn of the
twentieth century Meyer (1899) and Overton (1901) discovered that the anesthetic
potency of a group of compounds directly correlated with their solubility in a lipid
environment, specifically olive oil. Because membranes are largely lipid, the
natural conclusion was that anesthetics exerted their effects through actions on
lipids in membranes. Much later it was determined that critical, dynamic effects
in membranes occurred via proteins, and that hydrophobic regions within proteins
were “lipid-like” and hence able to bind anesthetic gas molecules by weak Van
der Waals forces. Most contemporary theories agree that anesthesia results from
alteration of dynamic, conformational functions of important brain neural
proteins: membrane ion channels, synaptic receptors, cytoskeleton,
neurotransmitter releasing mechanisms, and/or enzymes (Koplin and Eger 1979;
Kaufman, 1977; Eyring, Woodbury and D’Arrigo, 1973). Opinions and theories
disagree as to whether anesthetics alter these dynamic protein functions directly
via intra-protein hydrophobic pockets, or indirectly via membrane lipids
surrounding proteins, or at lipid protein interfaces (Franks and Lieb, 1982). There
is further disagreement as to whether a single, unitary mechanism can explain
actions of a wide range of anesthetic compounds acting on a presumably wide
range of neural proteins, as well as explain reversal of anesthesia by increased
pressure, and the paradoxical relationship between anesthetics and convulsants
(Halsey, 1976).
Correlations of anesthetic potency with solubility in “lipid-like” solvents
(olive oil, octanol, lecithin) are consistent with anesthetic effects occurring either
in lipids or in “lipid-like” hydrophobic pockets within proteins (Eger, Lundgren,
Miller and Stevens, 1969). Wulf and Featherstone (1957) were among the first to
demonstrate binding of anesthetics within hydrophobic regions of whale
myoglobin and other proteins. They suggested that anesthetic binding caused a
protein conformational change with a resultant increase in exposure of charged
groups at protein surfaces which sufficiently altered protein function to cause
anesthesia. Altered charge groups can change protein binding of surface water and
can explain the findings which led Pauling (1965) and Miller (1969) to propose
that anesthetic induced water-protein complexes (“clathrates”) were the cause of
anesthesia. Other research including Brammall, Beard and Hulands (1974)
demonstrated that anesthetics can cause conformational changes in functional
proteins, but at concentrations significantly higher than that required to cause
reversible clinical anesthesia.
A logical inference is that anesthetics, rather than causing protein
conformational changes, prevented those that were necessary for normal function.
Looking for model systems of functional dynamic activity in proteins, a number
of researchers have focused on a seemingly obscure group of systems which, on
the surface, are distantly removed from any semblance of cognitive function:
anesthetic inhibition of luminescence from photoproteins in firefly and a variety
of bacteria (Harvey, 1915; Halsey and Smith, 1970; White and Dundas, 1970).
Firefly luciferase is a protein dimer of about 100 kilodaltons (not unlike tubulin).
When combined with a 280 dalton hydrophobic molecule called luciferin, and in
the presence of ATP and oxygen, an excited electron state is induced which