gamma‐Aminobutyric‐acid‐ and pentobarbitone‐gated chloride currents in internally perfused frog sensory neurones.

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Abstract
GABA and pentobarbitone-induced Cl- currents (ICl) were studied in isolated frog sensory neurons after suppression of Na+, K+ and Ca2+ currents using a suction-pipette technique combining internal perfusion with voltage clamp. All GABA-sensitive neurons responded to pentobarbitone. Both GABA-and pentobarbitone-induced ICl reversed at the Cl- equilibrium potential (ECl). The dose-response curve for maxima of GABA-induced ICl was sigmoidal with a mean concentration producing a half-maximum response, Ka of 2 .times. 10-5 M at a Hill coefficient of 1.8. In the presence of pentobarbitone, the GABA-dose-response curve shifted to the left without affecting the saturating maximum current. At high concentrations, both GABA and pentobarbitone could also potentiate the pentobarbitone-and GABA-induced ICl, respectively, while pre-treatment with 1 of the 2 markedly attenuated currents induced by the other, indicating a cross-desensitization. In the presence of pentobarbitone, the augmented response was voltage dependent and this augmentation was much greater in the inward-current direction than outward. In producing ICl, pentobarbitone and its stereoisomers were potent in the order of (-) isomer > (.+-.) racemic mixture > (+) isomer. A stereospecific facilitatory action of pentobarbitone on GABA responses was also found in the same order. Responses to GABA, homotaurine, taurine, .beta.-alanine, 5-aminovaleric acid, (+)- and (-)-.gamma.-amino-.beta.-hydroxybutyric acid and muscimol were equally enhanced by pentobarbitone, though its action on glycine-induced ICl was less effective. Picrotoxin inhibited the GABA-and pentobarbitone-induced ICl from either side of membrane, while internal application of GABA and pentobarbitone did not exert any effect. Pentobarbitone binds to the barbiturate receptors located close to the GABA receptor-Cl- channel complex and directly affects the GAGA-GABA receptor interactions rather than the ionic channels.