gamma-Aminobutyric acid-stimulated chloride permeability in crayfish muscle

gamma-Aminobutyric acid selectively increased Cl- permeability in isolated strips of crayfish abdominal muscle. Muscle fibers incubated in Van Harrevald's solution at room temperature took up 36Cl- to the extent of 700 ml/kg wet weight with a halftime of 2.5 min. During 15-S incubations, the control 36Cl- uptake space was 131 +/- 4 ml/kg (n = 60) and this was significantly increased by gamma-aminobutyric acid at 200 muM or higher concentrations to 177 +/- 4 ml/kg (n = 48, P less than 0.05). This effect was specific for chloride since gamma-aminobutyric acid did not increase the uptake by crayfish muscle of radioactive sucrose, inositol, or propionate. gamma-Aminobutyric acid stimulation of 36Cl- uptake is mediated by receptor-ionophore function since the process shows pharmacological properties virtually identical to those observed by electrophysiological techniques. The gamma-aminobutyric acid stimulation of Cl- permeability is dose dependent with 50% of the maximal effect at 40 muM gamma-aminobutyric acid and the dose vs. response curve is somewhat sigmoid. The gamma-aminobutyric acid agonist muscimol causes the same maximal effect on Cl- uptake as gamma-aminobutyric acid, but acts at 5-fold lower concentrations, i.e. is more potent. However, the partial agonist gamma-amino, beta-hydroxybutyric acid produced little or no stimulation of 36Cl- flux. The response to gamma-aminobutyric acid was blocked by 2 mM beta-guanidinopropionate or gamma-guanidinobutyrate, 0.5 mM bicuculline, and 10 muM picrotoxinin. Picrotoxinin inhibition was dose dependent with 50% inhibition occurring at 4 muM. Antagonists did not affect control 36Cl- uptake. These results confirm electrophysiological observations that the postsynaptic response to the inhibitory neurotransmitter gamma-aminobutyric acid involves a rapid increase in membrane permeability to Cl-.