Kumamoto Health Science University, Japan.
Brain Res Bull. 2011 Jan 15;84(1):22-30. doi: 10.1016/j.brainresbull.2010.10.007. Epub 2010 Oct 29.
We investigated the functional roles of presynaptic GABA(A) receptors on excitatory nerve terminals in contributing to spontaneous and action potential-evoked glutamatergic transmission to rat hippocampal CA3 pyramidal neurons. Single CA3 neurons were mechanically isolated with adherent nerve terminals, namely the 'synaptic bouton preparation', and spontaneous glutamatergic excitatory synaptic potentials (sEPSCs) and EPSCs evoked by focal electrical stimuli of a single presynaptic glutamatergic boutons (eEPSCs) were recorded using conventional whole-cell patch recordings. Selective activation of presynaptic GABA(A) receptors on these excitatory nerve terminals by muscimol, markedly facilitated sEPSCs frequency but inhibited eEPSC amplitude. The facilitation of sEPSC frequency was completely occluded by GABA(A) receptor-Cl⁻ channel blockers bicuculline or penicillin (PN). PN itself concentration-dependently inhibited the GABA(A) receptor response induced by bath application of muscimol, but had no effect on the glutamate receptor response. In addition, pretreatment with a blocker of the Na(+), K(+), 2Cl⁻ co-transporter type 1 (NKCC-1), bumetanide, prevented the muscimol-induced inhibition of eEPSCs. The results indicate that activation of presynaptic GABA(A) receptors directly depolarizes glutamatergic excitatory nerve terminals and thereby differentially modulates sEPSCs and eEPSCs.
我们研究了突触前 GABA(A) 受体在兴奋性神经末梢中的功能作用，这些受体有助于向大鼠海马 CA3 锥体神经元传递自发性和动作电位诱发的谷氨酸能传递。使用传统的全细胞膜片钳记录，通过粘着性神经末梢机械分离单个 CA3 神经元，即“突触小泡制备”，并记录单个突触前谷氨酸能小泡（eEPSCs）引发的自发性谷氨酸能兴奋性突触后电位（sEPSCs）和 EPSCs。通过 muscimol 选择性激活这些兴奋性神经末梢上的突触前 GABA(A) 受体，明显增加了 sEPSC 的频率，但抑制了 eEPSC 的幅度。GABA(A) 受体-Cl⁻通道阻滞剂毒蕈碱或青霉素（PN）完全阻断了 sEPSC 频率的增加。PN 本身浓度依赖性地抑制了浴用 muscimol 诱导的 GABA(A) 受体反应，但对谷氨酸受体反应没有影响。此外，Na(+)、K(+)、2Cl⁻共转运体 1（NKCC-1）的阻滞剂布美他尼预处理可防止 muscimol 诱导的 eEPSC 抑制。结果表明，激活突触前 GABA(A) 受体可直接使谷氨酸能兴奋性神经末梢去极化，从而差异调节 sEPSC 和 eEPSC。
