Takebayashi M, Kagaya A, Hayashi T, Motohashi N, Yamawaki S
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
Eur J Pharmacol. 1996 Feb 15;297(1-2):137-43. doi: 10.1016/0014-2999(95)00734-2.
The effect of gamma-aminobutyric acid (GABA) on intracellular Ca2+ concentration ([Ca2+]i) in cultured prenatal rat cortical neurons was investigated using fluorescence imaging. GABA or muscimol, but not baclofen, increased [Ca2+]i in a dose-dependent manner. The GABAA receptor antagonists, bicuculline and picrotoxin, inhibited the GABA response. Furosemide, an inhibitor of the Na+/K+/2Cl- cotransporter, inhibited the GABA response in a noncompetitive manner. Ethacrynic acid, an inhibitor of an ATP-dependent Cl- pump, also inhibited the GABA-induced increased in [Ca2+]i. These results suggest a role for Cl- transport processes in the GABA response. The coapplication of GABA and high K+ led to a non-additive increase in the GABA response. The GABA response was also inhibited by nifedipine, a voltage-gated Ca2+ channel blocker, and abolished by the absence of extracellular Ca2+. Results indicate that the GABA response shares a common pathway of Ca2+ movement with the high K(+)-induced response. These observations suggest that the stimulation with GABA results in Ca2+ influx through voltage-gated Ca2+ channels, and that these effects are dependent on Cl- transport systems.
利用荧光成像技术研究了γ-氨基丁酸（GABA）对培养的产前大鼠皮质神经元细胞内钙离子浓度（[Ca2+]i）的影响。GABA或蝇蕈醇，但不是巴氯芬，以剂量依赖性方式增加[Ca2+]i。GABAA受体拮抗剂荷包牡丹碱和印防己毒素抑制了GABA反应。呋塞米，一种Na+/K+/2Cl-协同转运蛋白抑制剂，以非竞争性方式抑制GABA反应。依他尼酸，一种ATP依赖性Cl-泵抑制剂，也抑制了GABA诱导的[Ca2+]i增加。这些结果表明Cl-转运过程在GABA反应中起作用。GABA和高钾共同应用导致GABA反应的非累加性增加。GABA反应也被硝苯地平（一种电压门控Ca2+通道阻滞剂）抑制，并且在没有细胞外Ca2+的情况下被消除。结果表明，GABA反应与高钾诱导的反应共享Ca2+移动的共同途径。这些观察结果表明，GABA刺激导致Ca2+通过电压门控Ca2+通道内流，并且这些效应依赖于Cl-转运系统。
