Blocking effect of 1-naphthyl acetyl spermine on Ca2+-permeable AMPA receptors in cultured rat hippocampal neurons
Blocking effect of 1-naphthyl acetyl spermine on Ca2+-permeable AMPA receptors in cultured rat hippocampal neurons
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DOI：
10.1016/s0168-0102(97)00067-9
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发表时间：
1997-09-01
影响因子：
2.9
通讯作者：
Ozawa, S
中科院分区：
文献类型：
--
作者：
Koike, M;Iino, M;Ozawa, S
用全细胞膜片钳技术研究了Joro蜘蛛毒素（Joro spider toxin，JSTX）的人工合成类似物1-萘基乙酰精胺（1-naphthyl acetyl spermine，NASPM）对培养的大鼠海马神经元α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid，AMPA）型谷氨酸受体的作用。培养的神经元的人口AMPA受体具有强大的内向整流和高渗透性的Ca 2+（II型神经元），而大多数神经元（I型神经元）的AMPA受体轻微向外整流和小Ca 2+渗透性。NASPM选择性地抑制内向整流和Ca 2+渗透AMPA受体在II型神经元中表达。它对I型神经元中的AMPA受体没有影响。NASPM对Ca ~（2+）可透过的AMPA受体的阻断作用具有使用和电压依赖性。当NASPM的作用达到稳态时，在II型神经元中由红藻氨酸盐（AMPA受体的非脱敏激动剂）的离子电渗应用诱导的电流响应在-60 mV下以剂量依赖性方式被NASPM抑制（IC 50 0.33 μ M，Hill系数0.94）。对红藻氨酸的反应在冲洗NASPM后部分恢复。当神经元膜电位高于+40 mV时，NASPM不影响Ca 2+渗透性AMPA受体。此外，通过将膜电位转移到+60 mV持续5 s，连同红藻氨酸盐的单次离子电渗应用，在负电位下获得的NASPM的阻断被瞬时去除。NASPM将是一个有用的药理学工具，阐明生理和病理意义的Ca 2+渗透AMPA受体在中枢神经系统。(C)1997 Elsevier Science爱尔兰有限公司
Effects of 1-naphthyl acetyl spermine (NASPM), a synthetic analogue of Joro spider toxin (JSTX), on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors were studied in cultured rat hippocampal neurons using the whole-cell patch clamp technique. A population of cultured neurons had AMPA receptors with a strong inward rectification and a high permeability to Ca2+ (type II neurons), whereas most neurons (type I neurons) had AMPA receptors with a slight outward rectification and little Ca2+ permeability. NASPM selectively suppressed the inwardly rectifying and Ca2+-permeable AMPA receptors expressed in type II neurons. It had no effect on AMPA receptors in type I neurons. The blocking effect of NASPM on the Ca2+-permeable AMPA receptors was use and voltage-dependent. When the effect of NASPM reached a steady state, current responses induced by ionophoretic applications of kainate, a non-desensitizing agonist of AMPA receptors, in type II neurons were suppressed by NASPM in a dose-dependent manner at -60 mV (IC50 0.33 mu M, and Hill coefficient 0.94). The response to kainate recovered partially after washing out NASPM. NASPM did not affect the Ca2+-permeable AMPA receptors when the neuronal membrane was held at potentials more positive than +40 mV. Furthermore, the blockade by NASPM which was attained at negative potentials was transiently removed by shifting membrane potential to + 60 mV for 5 s together with a single ionophoretic application of kainate. NASPM would be useful as a pharmacological tool for elucidating both physiological and pathological significances of Ca2+-permeable AMPA receptors in the CNS. (C) 1997 Elsevier Science Ireland Ltd.