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  • Title: Modulation of gamma-aminobutyric acid receptor-channel complex by alcohols.
    Author: Nakahiro M, Arakawa O, Narahashi T.
    Journal: J Pharmacol Exp Ther; 1991 Oct; 259(1):235-40. PubMed ID: 1656020.
    Abstract:
    The electrophysiological effects of ethanol on the gamma-aminobutyric acid (GABA) system have been a matter of controversies; some observed an enhancement of GABA response whereas others failed to see the effect. Acute effects of n-alcohols (ethanol, n-butanol, n-hexanol and n-octanol) on chloride current activated by bath application of GABA were studied with the rat dorsal root ganglion neurons maintained in primary culture. The whole-cell patch-clamp technique was used to record the current. Ethanol (30-300 mM), n-butanol (1-30 mM), n-hexanol (30-1000 microM) and n-octanol (3-100 microM) enhanced the initial peak current evoked by 30 microM GABA in a dose-dependent manner. The potency of alcohols increased with the chain length and was well correlated with the membrane/buffer partition coefficient. The observed low potency of ethanol is also predicted from this correlation. The dose-response curve for the GABA-induced nondesensitized current was sigmoidal with an apparent dissociation constant of 55 microM and a Hill coefficient of 1.5 to 1.9. Ethanol (300 mM) and n-octanol (100 microM) shifted the dose-response curve in the direction of low concentration without greatly changing the Hill coefficient. Ethanol (300 mM) and n-octanol (30 and 100 microM) shortened the decay time course of the current induced by 30 microM GABA to 66, 74 and 52% of control, respectively. Unlike the peak nondesensitized current, the desensitized steady-state current induced by high concentration (300 microM) of GABA was suppressed by long-chain alcohols.(ABSTRACT TRUNCATED AT 250 WORDS)
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