Ion channel modulation as the basis for general anesthesia.
(1) Modulation of the function of the GABA(A) and neuronal nicotinic acetylcholine receptor channels caused by general anesthetics and modulation of the GABA(A) receptor-channel by halothane, enflurane, isoflurane, and n-octanol was channel state-dependent. (3) Halothane modulation of the GABA(A) receptor was independent of subunits, but n-octanol modulation was subunit-dependent. (4) Ethanol at 30-100 microM was very potent in accelerating the desensitization of currents induced by acetylcholine. (5) The ethanol modulation was subunit- and state-dependent, occurring in the alpha3beta4 combination but only weakly in the alpha3beta2 combination. (6) In contrast, halothane at 430 microM (approximately 1 MAC) potently suppressed ACh-induced currents in the alpha3beta2 subunit combination.
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611-3008, USA. tna597@anima.nums.nwu.edu
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T
Narahashi
G L
GL
Aistrup
J M
JM
Lindstrom
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W
Marszalec
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K
Nagata
F
F
Wang
J Z
JZ
Yeh
D000768:Anesthesia, General; D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007473:Ion Channels / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000737:chemistry / Q000187:drug effects
D018681:Anesthetics, General; D007473:Ion Channels; D011963:Receptors, GABA-A