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J. Biol. Chem., Vol. 278, Issue 45, 44097-44102, November 7, 2003

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A Rapid Increase in the Total Number of Cell Surface Functional GABA_A Receptors Induced by Brain-derived Neurotrophic Factor in Rat Visual Cortex^*

Yoshito Mizoguchi, Takashi Kanematsu, Masato Hirata, and Junichi Nabekura¶

From the Cellular and Systems Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 and the Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan

The number of postsynaptic -aminobutyric acid type A (GABA_A) receptors is a fundamental determinant of the variability of inhibitory synaptic responses in the central nervous system. In rat visual cortex, [³H]SR-95531 binding assays revealed that brain-derived neurotrophic factor (BDNF), one of the neurotrophins, induced a rapid increase in the total number of cell surface GABA_A receptors, through the activation of Trk B receptor tyrosine kinases. We also demonstrated that BDNF rapidly induced a sustained potentiation of GABA_A receptor-mediated currents, using nystatin-perforated patch clamp recordings, in visual cortical layer 5 pyramidal neurons freshly isolated from P14 rats. The potentiation was caused by the activation of Trk B receptor tyrosine kinase and phospholipase C-. In addition, intracellular Ca²⁺ was important for the potentiation of GABA_A responses induced by BDNF. The selective increase in mean miniature inhibitory postsynaptic (mIPSC) current amplitude without effects on mIPSC time courses supports the idea that BDNF rapidly induces an increase in the total number of cell surface functional GABA_A receptors in visual cortical pyramidal neurons. These results suggest that BDNF could alter the number of cell surface GABA_A receptors in a region-specific manner.

Received for publication, June 4, 2003 , and in revised form, August 25, 2003.

^* This work was supported by Grants-in-aid for Scientific Research on Priority Areas (C)-Advanced Brain Project (15016082) and Research Grants (15390065, 15650076) from the Ministry of Education, Culture, Sports, and Science and Technology, Japan to J. Nabekura. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed. Tel.: 81-92-642-6090; Fax: 81-92-642-6094; E-mail: nabekura{at}mailserver.med.kyushu-u.ac.jp.

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