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The Journal of Neuroscience, March 15, 2000, 20(6):2166-2174
Regulation of Kinetic Properties of GluR2 AMPA Receptor Channels by Alternative Splicing
Maki Koike1, 2, Shota Tsukada1, Keisuke Tsuzuki1, 2, Hiromasa Kijima3, and Seiji Ozawa1, 2 1 Department of Physiology, Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan, 2 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan, and 3 Department of Physics, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan
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 Xenopus oocytes 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.
Key words: AMPA receptor channel; GluR2; flip/flop splice variants; Q/R site; desensitization; deactivation
Copyright © 2000 Society for Neuroscience 0270-6474/00/2062166-09$05.00/0
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