Functional Correlation of NMDA Receptor epsilon  Subunits Expression with the Properties of Single-Channel and Synaptic Currents in the Developing Cerebellum

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Volume 16, Number 14, Issue of July 15, 1996 pp. 4376-4382
Copyright ©1996 Society for Neuroscience

Functional Correlation of NMDA Receptor $epsilon$ Subunits Expression with the Properties of Single-Channel and Synaptic Currents in the Developing Cerebellum

Received Feb. 26, 1996; revised April 26, 1996; accepted May 1, 1996.
Tomoyuki Takahashi¹, Dirk Feldmeyer⁴, Norimitsu Suzuki¹, Kayoko Onodera¹, Stuart G. Cull-Candy⁴, Kenji Sakimura³, and Masayoshi Mishina²
¹ Department of Neurophysiology, Institute for Brain Research and ² Department of Pharmacology, Faculty of Medicine, University of Tokyo, 113 Tokyo, Japan, ³ Department of Neuropharmacology, Brain Research Institute, Niigata University, Niigata 951, Japan, and ⁴ Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom
NMDA receptor (NMDAR) subunits $epsilon$ 1- $epsilon$ 4 are expressed differentially with respect to brain region and ontogenic period, but their functional roles still are unclear. We have compared an $epsilon$ 1 subunit-ablated mutant mouse with the wild-type to characterize the effect of $epsilon$ subunit expression on NMDAR-mediated single-channel currents and synaptic currents of granule cells in cerebellar slices. Single-channel and Western blot analyses indicated that the $epsilon$ 2 subunit disappeared gradually during the first postnatal month in both wild-type and mutant mice. Concomitantly, the voltage-dependent Mg²⁺ block of NMDAR-mediated EPSCs (NMDA-EPSCs) was decreased. Throughout the developmental period studied, postnatal day 7-24 (P7-P24), the decay time course of NMDA-EPSCs in $epsilon$ 1 mutant ( $-$ / $-$ ) mice was slower than in wild-type mice. We suggest that the expression of the $epsilon$ 3 subunit late in development is responsible for a reduction in the sensitivity of NMDA-EPSCs to block by extracellular Mg²⁺ and that receptors containing the $epsilon$ 1 subunit determine the fast kinetics of the NMDA-EPSCs.

Key words: NMDA receptor; synaptic current; single channel; cerebellum; gene targeting; patch clamp

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