Steroid modulation of the strychnine-sensitive glycine receptor

Electrophysiological responses to glycine (0.25-5 mM) were obtained on preparations of rat optic nerve. The log dose-response curve for glycine was shifted to the left by a factor of 2 by 1 microM 20 alpha-dihydrocortisol and by a factor of about 1.5 by 1 microM alpha-cortol and 10 microM hydrocortisone. A similar effect was obtained with 100 microM chlormethiazole but the GABA-potentiating steroid alphaxalone (1 microM) was ineffective on responses to glycine. 20 alpha-Dihydrocortisol and chlormethiazole also appeared to increase the antagonistic potency of strychnine against glycine. These observations suggest that the active steroids and chlormethiazole increase the functional interaction of both glycine and strychnine with the glycine-gated chloride channel.