Voltage-clamp studies of the inhibition of gamma-aminobutyric acid response by glucocorticoids in bullfrog primary afferent neurons.
Acute effects of glucocorticoids on the response to gamma-aminobutyric acid (GABA) were examined in primary afferent neurons in bullfrog spinal ganglia, using intracellular and voltage-clamp recording techniques. Prednisolone and hydrocortisone (5 microM to 1 mM) caused a dose-dependent decrease in the amplitude of GABA-induced depolarization, while having no effect on the membrane potential and resistance of the neuron. Prednisolone depressed the muscimol-induced depolarization. Nipecotic acid, a blocker of GABA uptake, did not influence the inhibitory action of prednisolone. Voltage-clamp analyses showed that the inward current induced by an iontophoretic application of GABA (GABA current) was suppressed by prednisolone and hydrocortisone. The depression of the GABA current is neither due to a blockage of open channels nor a facilitation of the desensitization of GABA receptors. Prednisolone shifted the dose-response curve of the GABA current downward. The double-reciprocal (Lineweaver-Burk) plot showed that the maximum GABA current was reduced by prednisolone, suggesting a non-competitive antagonism. These results suggest that glucocorticoids suppress the GABA-induced chloride current, decreasing the number of functional channels associated with GABAA receptor.
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D018756:GABA Antagonists; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology*; D011892:Rana catesbeiana; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D001640:Bicuculline; D018756:GABA Antagonists; D010852:Picrotoxin; D011239:Prednisolone; D005680:gamma-Aminobutyric Acid