大鼠海马神经元中突触N-甲基-D-天冬氨酸受体的动力学和药理学特性调控取决于突触前胞吐作用。

Regulation of kinetic and pharmacological properties of synaptic NMDA receptors depends on presynaptic exocytosis in rat hippocampal neurones.

Lindlbauer R, Mohrmann R, Hatt H, Gottmann K

Lehrstuhl fur Zellphysiologie, ND4, Ruhr-Universitat Bochum, D-44780 Bochum, Germany.

J Physiol. 1998 Apr 15;508 ( Pt 2)(Pt 2):495-502. doi: 10.1111/j.1469-7793.1998.00495.x.

Abstract

Using whole-cell patch-clamp recordings of NMDA EPSCs from co-cultured rat hippocampal (CA region) neurones, developmental changes in the kinetic and pharmacological properties of synaptic NMDA receptors were investigated. During in vitro differentiation a fast decaying component increasingly contributed to NMDA EPSCs. 2. Extracellular Mg2+ (1 mM) strongly blocked NMDA EPSCs at all stages in culture. Using the NR2B subunit-specific NMDA receptor antagonist ifenprodil (3 microM), we observed a developmental decrease in ifenprodil sensitivity of NMDA EPSCs. This suggests developmental changes in the expression of NMDA receptor subtypes. 3. To transiently block presynaptic exocytosis, we incubated presynaptic explants with tetanus toxin (TeTx) prior to cultivation. In TeTx-pretreated cultures the occurrence of fast decaying components of NMDA EPSCs and the developmental decrease in ifenprodil sensitivity was inhibited. Our results indicate a regulatory role of presynaptic exocytosis in the expression of NMDA receptor subtypes.

摘要

利用共培养大鼠海马（CA区）神经元的NMDA兴奋性突触后电流（EPSCs）的全细胞膜片钳记录，研究了突触NMDA受体动力学和药理学特性的发育变化。在体外分化过程中，快速衰减成分对NMDA EPSCs的贡献越来越大。2. 细胞外Mg2+（1 mM）在培养的所有阶段都强烈阻断NMDA EPSCs。使用NR2B亚基特异性NMDA受体拮抗剂ifenprodil（3 microM），我们观察到NMDA EPSCs对ifenprodil的敏感性在发育过程中降低。这表明NMDA受体亚型的表达发生了发育变化。3. 为了短暂阻断突触前胞吐作用，我们在培养前用破伤风毒素（TeTx）孵育突触前外植体。在TeTx预处理的培养物中，NMDA EPSCs快速衰减成分的出现以及ifenprodil敏感性的发育性降低受到抑制。我们的结果表明突触前胞吐作用在NMDA受体亚型表达中的调节作用。