Vitten Harald, Reusch Margret, Friauf Eckhard, Löhrke Stefan
Animal Physiology Group, Department of Biology, University of Kaiserslautern, Germany.
J Neurobiol. 2004 Jun;59(3):272-88. doi: 10.1002/neu.10326.
A functional analysis of AMPA and kainate receptors (AMPARs and KARs) in the lateral superior olive (LSO), a major nucleus in the auditory brainstem, has not been performed so far, to our knowledge. Here we investigated the presence and characteristics of such receptors in the rat LSO by means of whole-cell patch-clamp recordings in combination with pharmacology. Current responses evoked by 200 microM AMPA were completely blocked by the specific AMPAR antagonist GYKI 52466 (100 microM). Properties of the AMPAR-mediated currents (latency, activation time constant, and peak amplitude) remained constant between postnatal day 3 (P3) and P10. Current responses evoked by 100 microM KA were not completely blocked by 100 microM GYKI 52466, indicating that the residual component was mediated by KARs. Throughout development, two groups of KAR-mediated currents (fast I(KA) and slow I(KA)) were distinguished because they had significantly different mean activation time constants. Moreover, the mean peak amplitude of fast I(KA) was significantly higher than that of slow I(KA). The differentiation into fast I(KA) and slow I(KA) can be explained by the existence of two groups of LSO neurons displaying different KAR densities, distributions, and/or diverse types with differences in conductance. Application of the specific KAR subunit agonists SYM 2081 (10 microM), ATPA (10 microM), or iodowillardiine (1 microM) evoked currents in almost all cells tested, showing that GluR5 subunits are a component of functional KARs in LSO neurons. Electrical stimulation of ipsilateral input fibers in the presence of KAR antagonists (NS-102 and GAMS), modulators (WGA), or GYKI 52466 revealed the presence of synaptic KARs in LSO neurons.
据我们所知,目前尚未对听觉脑干中的主要核团——外侧上橄榄核(LSO)中的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)和海人藻酸受体(AMPARs和KARs)进行功能分析。在此,我们通过全细胞膜片钳记录结合药理学方法,研究了大鼠LSO中此类受体的存在情况及其特性。200微摩尔AMPA诱发的电流反应被特异性AMPAR拮抗剂GYKI 52466(100微摩尔)完全阻断。在出生后第3天(P3)至第10天之间,AMPAR介导的电流特性(潜伏期、激活时间常数和峰值幅度)保持恒定。100微摩尔海人藻酸(KA)诱发的电流反应未被100微摩尔GYKI 52466完全阻断,这表明残余成分是由KARs介导的。在整个发育过程中,可区分出两组KAR介导的电流(快速I(KA)和慢速I(KA)),因为它们的平均激活时间常数显著不同。此外,快速I(KA)的平均峰值幅度明显高于慢速I(KA)。快速I(KA)和慢速I(KA)的分化可以通过存在两组显示不同KAR密度、分布和/或具有不同电导类型的LSO神经元来解释。应用特异性KAR亚基激动剂SYM 2081(10微摩尔)、ATPA(10微摩尔)或碘海葱苷(1微摩尔)在几乎所有测试细胞中都诱发了电流,表明GluR5亚基是LSO神经元中功能性KARs的一个组成部分。在存在KAR拮抗剂(NS-102和GAMS)、调节剂(WGA)或GYKI 52466的情况下,对同侧输入纤维进行电刺激,揭示了LSO神经元中存在突触KARs。