Melatonin potentiates the GABA(A) receptor-mediated current in cultured chick spinal cord neurons.

The effect of melatonin on the gamma-aminobutyric acidA (GABA(A)) receptor-mediated response was studied in cultured chick spinal cord neurons using the whole-cell voltage-clamp recording technique. Melatonin rapidly and reversibly potentiated the GABA-induced current in a dose-dependent fashion, with an EC50 of 766 microM and a maximal potentiation of 148%. Potentiation of the GABA response by melatonin was mediated by increasing the potency of GABA rather than the efficacy. Prolonged exposure to a saturating concentration of the disulfide-reducing agent dithiothreitol did not attentuate the effect of melatonin on the GABA response, indicating that melatonin does not act through the redox site. Furthermore, our results demonstrate that melatonin and 5alpha-pregnan-3alpha-ol-20-one (a positive steroid modulator of the GABA(A) receptor) act through different sites.