Regulation of Kinetic Properties of GluR2 AMPA Receptor Channels by Alternative Splicing
Regulation of Kinetic Properties of GluR2 AMPA Receptor Channels by Alternative Splicing
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通过选择性剪接调节 GluR2 AMPA 受体通道的动力学特性
DOI：
10.1523/jneurosci.20-06-02166.2000
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Seiji Ozawa
中科院分区：
文献类型：
--
作者：
M. Koike;Shota Tsukada;K. Tsuzuki;H. Kijima;Seiji Ozawa
AMPA型谷氨酸受体的四个亚基（GluR 1-GluR 4或GluR-A-GluR-D）以两种不同的形式存在，翻转和翻转，由115 bp区域的选择性剪接产生。GluR 2亚基在确定AMPA受体通道的功能特性中起关键作用。在这项研究中，我们研究了使用快速激动剂应用技术在异种卵母细胞中表达的GluR 2亚基的翻转和翻转剪接变体之间的动力学特性的差异。用压电驱动的双管应用移液管将谷氨酸施加到来自卵母细胞的外向贴片上。因为由编辑形式的GluR 2（GluR 2 R）组成的同源受体通道不产生可感知的电流响应，所以我们在卵母细胞中表达了未编辑形式的GluR 2（GluR 2 Q），其产生了足以用于动力学性质分析的大电流响应。在施加1 mm谷氨酸盐期间的脱敏时间常数在翻转中为5.89 ± 0.17毫秒（n = 50），在翻转中为1.18 ± 0.05毫秒（n = 37）。失活时间常数在翻转中为0.62 ± 0.06毫秒（n = 10），在翻转中为0.54 ± 0.05毫秒（n = 10）。稳态非减敏电流为翻转时峰值电流的6.8 ± 0.4%（n = 53），而翻转时几乎可以忽略不计，仅为1.1 ± 0.1%（n = 36）。在GluR 2 Q/GluR 2 R组装的异聚体受体中也观察到翻转变体中较慢的脱敏动力学和较大的稳态电流响应。因此，脱敏发生在重组GluR 2受体通道的flop变体中更为突出。
The four subunits of the AMPA-type glutamate receptor (GluR1–GluR4 or GluR-A–GluR-D) exist in two distinct forms, flip and flop, generated by alternative splicing of a 115 bp region. The GluR2 subunit plays a key role in determining the functional properties of the AMPA receptor channel. In this study, we examined the differences in kinetic properties between the flip and flop splice variants of the GluR2 subunit expressed in Xenopusoocytes using fast agonist application techniques. Glutamate was applied to outside-out patches from oocytes with piezo-driven double-barreled application pipettes. Because homomeric receptor channels composed of the edited form of GluR2 (GluR2R) produce no appreciable current responses, we expressed the unedited form of GluR2 (GluR2Q) in oocytes, which produced large current responses sufficient for analysis of the kinetic properties. The time constant for desensitization during application of 1 mm glutamate was 5.89 ± 0.17 msec (n = 50) in flip and 1.18 ± 0.05 msec (n = 37) in flop. The deactivation time constant was 0.62 ± 0.06 msec (n = 10) in flip and 0.54 ± 0.05 msec (n = 10) in flop. The steady-state nondesensitizing current was 6.8 ± 0.4% (n = 53) of the peak current in flip, whereas it was almost negligible in flop, being only 1.1 ± 0.1% (n = 36). The slower desensitization kinetics and larger steady-state current responses in the flip variant were also observed in heteromeric receptors assembled from GluR2Q/GluR2R. Thus, desensitization occurred much more prominently in the flop variant in the recombinant GluR2 receptor channels.
影响因子：
3.4
作者：
RAMAN, IM;TRUSSELL, LO
通讯作者：
TRUSSELL, LO
影响因子：
56.9
作者：
CLEMENTS, JD;LESTER, RAJ;WESTBROOK, GL
通讯作者：
WESTBROOK, GL