Modulation of GABAA and glycine receptors by chlormethiazole.
The influence of chlormethiazole, on currents evoked by gamma-aminobutyric acid (GABA) and glycine, was investigated under voltage-clamp conditions, in bovine chromaffin cells and murine spinal neurones, respectively. Chlormethiazole (30 and 100 microM) dose dependently potentiated currents activated by either inhibitory neurotransmitter. The potentiation of the GABA-evoked response occurred without altering the reversal potential and was not influenced by the benzodiazepine receptor antagonist Ro 15-1788 (300 nM). GABA-gated channels, recorded from outside-out membrane patches, showed increased probability of being in the conducting state in the presence of chlormethiazole. High concentrations of chlormethiazole (3 mM) activated bicuculline (1 microM)-sensitive whole-cell currents with a reversal potential similar to the chloride equilibrium potential. Chlormethiazole potentiates GABA- and glycine-activated currents and at higher doses, directly activates the GABAA receptor.
Hales
T G
TG
Department of Anesthesiology, Medical Center, UCLA 90024.
Lambert
J J
JJ
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002719:Chlormethiazole / Q000494:pharmacology*; D002838:Chromaffin System / Q000187:drug effects; D004357:Drug Synergism; D004558:Electric Stimulation; D004594:Electrophysiology; D005998:Glycine / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011963:Receptors, GABA-A; D002719:Chlormethiazole; D005680:gamma-Aminobutyric Acid; D005998:Glycine