Glykys Joseph, Mody Istvan
Interdepartmental PhD Program for Neuroscience and Departments of Neurology and Physiology, The David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, USA.
J Physiol. 2007 Aug 1;582(Pt 3):1163-78. doi: 10.1113/jphysiol.2007.134460. Epub 2007 May 24.
The extracellular space of the brain contains gamma-aminobutyric acid (GABA) that activates extrasynaptic GABA(A) receptors mediating tonic inhibition. The source of this GABA is uncertain: it could be overspill of vesicular release, non-vesicular leakage, reverse transport, dying cells or glia. Using a novel approach, we simultaneously measured phasic and tonic inhibitory currents and assessed their correlation. Enhancing or diminishing vesicular GABA release in hippocampal neurons caused highly correlated changes in the two inhibitions. During high-frequency phasic inhibitory bursts, tonic current was also enhanced as shown by simulating the summation of IPSCs and by recordings in knockout mice devoid of tonic inhibitory current. When vesicular release was reduced by blocking action potentials or the vesicular GABA transporter, phasic and tonic currents decreased in a correlated fashion. Our results are consistent with most of hippocampal tonic inhibitory current being mediated by GABA released from the very vesicles responsible for activating phasic inhibition.
大脑的细胞外空间含有γ-氨基丁酸（GABA），它可激活介导张力性抑制的突触外GABA(A)受体。这种GABA的来源尚不确定：它可能是囊泡释放的溢出、非囊泡泄漏、逆向转运、死亡细胞或神经胶质细胞。我们采用一种新方法，同时测量了相位性和张力性抑制电流，并评估了它们之间的相关性。增强或减少海马神经元中囊泡GABA的释放会导致两种抑制作用发生高度相关的变化。在高频相位性抑制爆发期间，通过模拟抑制性突触后电流（IPSC）的总和以及在缺乏张力性抑制电流的基因敲除小鼠中进行记录表明，张力性电流也会增强。当通过阻断动作电位或囊泡GABA转运体来减少囊泡释放时，相位性和张力性电流会以相关方式降低。我们的结果与大多数海马张力性抑制电流由负责激活相位性抑制的囊泡释放的GABA介导这一观点一致。
