Ticku M K, Olsen R W
Biochim Biophys Acta. 1977 Feb 4;464(3):519-29. doi: 10.1016/0005-2736(77)90027-x.
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-.
γ-氨基丁酸可选择性地增加离体小龙虾腹肌条的氯离子通透性。在室温下于范哈勒瓦尔德氏溶液中孵育的肌纤维摄取³⁶Cl⁻的量达到700毫升/千克湿重，半衰期为2.5分钟。在15秒的孵育期间，对照的³⁶Cl⁻摄取空间为131±4毫升/千克（n = 60），而在200μM或更高浓度的γ-氨基丁酸作用下，该值显著增加至177±4毫升/千克（n = 48，P<0.05）。这种作用对氯离子具有特异性，因为γ-氨基丁酸不会增加小龙虾肌肉对放射性蔗糖、肌醇或丙酸盐的摄取。γ-氨基丁酸对³⁶Cl⁻摄取的刺激作用是由受体-离子载体功能介导的，因为该过程显示出与通过电生理技术观察到的药理学特性几乎相同。γ-氨基丁酸对氯离子通透性的刺激作用呈剂量依赖性，在40μMγ-氨基丁酸时达到最大效应的50%，剂量-反应曲线呈S形。γ-氨基丁酸激动剂蝇蕈醇对氯离子摄取的最大效应与γ-氨基丁酸相同，但作用浓度低5倍，即效力更强。然而，部分激动剂γ-氨基-β-羟基丁酸对³⁶Cl⁻通量几乎没有或没有刺激作用。对γ-氨基丁酸的反应被2 mMβ-胍基丙酸或γ-胍基丁酸、0.5 mM荷包牡丹碱和10μM印防己毒素阻断。印防己毒素的抑制作用呈剂量依赖性，在4μM时出现50%的抑制。拮抗剂不影响对照的³⁶Cl⁻摄取。这些结果证实了电生理观察结果，即对抑制性神经递质γ-氨基丁酸的突触后反应涉及膜对氯离子通透性的快速增加。
