Chloride current induced by alcohols in rat dorsal root ganglion neurons.
We have recently demonstrated that ethanol and longer-chain alcohols (n-alcohols) enhance gamma-aminobutyric acid (GABA)-induced chloride currents before desensitization takes place. The potencies of n-alcohols increase with lengthening of the carbon chain. We now report that n-alcohols induce chloride currents by themselves in rat dorsal root ganglion neurons in primary culture. The whole cell variation of the patch clamp techniques was used to record currents as induced by external application of alcohols and other test compounds. Ethanol, n-butanol, n-hexanol and n-octanol induced inward currents with their potencies increasing in that order. The potencies were approximately one order of magnitude less than those to augment GABA-induced currents. The maximum amplitudes of currents induced by the alcohols were less than those produced by GABA. The n-octanol-induced currents were carried largely by chloride ions because the reversal potentials were changed according to the Nernst chloride potential as the internal chloride concentration was changed. Bicuculline and picrotoxin suppressed the n-octanol-induced current, and chlordiazepoxide and pentobarbital augmented the n-octanol-induced current. Therefore, the alcohol-induced chloride currents flow through the chloride channels associated with the GABAA receptors. When applied after the GABA-induced current was desensitized to a lower level, n-octanol suppressed rather than augmented the current. Thus, n-alcohols mimic barbiturates in augmenting the GABA-induced currents and in generating chloride currents by themselves. These actions of both agents may play a role in causing anxiolytic, sedative and/or anesthetic effects.
Arakawa
O
O
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
Nakahiro
M
M
Narahashi
T
T
D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D002707:Chlordiazepoxide / Q000494:pharmacology; D018118:Chloride Channels; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005727:Ganglia, Spinal / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000438:Alcohols; D001640:Bicuculline; D002707:Chlordiazepoxide; D018118:Chloride Channels; D007473:Ion Channels; D008565:Membrane Proteins; D010424:Pentobarbital; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid