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Vol. 284, Issue 3, 934-942, March 1998
1 Receptors1
Departments of
Anesthesia and Critical Care (S.E.F., Q.Y., N.L.H.)
and
Pharmacological and Physiological Sciences (N.L.H.) and
Committee
on Neurobiology (M.D.K.), University of Chicago, Chicago,
Illinois
The actions of 2,2,2,-trichloroethanol were studied on
agonist-activated Cl
currents in 
-aminobutyric acid
type A (GABAA), glycine and GABA 
1 receptors
by use of the whole-cell patch-clamp technique. Recombinant wild-type
and mutant receptor subunits were transiently expressed in human
embryonic kidney (HEK) 293 cells. Trichloroethanol enhanced currents
elicited by submaximal (EC20) agonist concentrations at
GABAA 
2
1 receptors and
glycine 1 homomeric receptors in a reversible,
concentration-dependent manner. Trichloroethanol, at concentrations of
2 mM, did not significantly alter the magnitude of submaximal GABA
currents at GABA 1 receptors, whereas higher concentrations inhibited submaximal GABA currents. Recent work has
identified residues within putative transmembrane domains 2 and 3 as
critical for positive modulation of GABAA and glycine receptors by n-alkanols and volatile ether anesthetics.
Submaximal glycine currents at receptors containing either of two
specific mutations within the glycine receptor 1 subunit
(S267I and A288W) were not enhanced by low
concentrations of trichloroethanol and were inhibited by higher
concentrations of trichloroethanol. In the GABAA
21 receptor, a specific mutation within
transmembrane domain 3 of the 1 subunit
(M286W) also abolished positive modulation by
trichloroethanol. Mutations within the GABAA
2 receptor subunit did not alter positive modulation by
TCEt, whereas such mutations ablate positive modulation by n-alkanols and volatile anesthetics. In summary,
trichloroethanol modulation of GABAA, glycine and GABA
1 receptors shares some, but not all, features in common
with the requirements for modulation by n-alkanols and
volatile anesthetics.
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