PMID- 12941963 OWN - NLM STAT- MEDLINE DCOM- 20040105 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 278 IP - 45 DP - 2003 Nov 7 TI - A rapid increase in the total number of cell surface functional GABAA receptors induced by brain-derived neurotrophic factor in rat visual cortex. PG - 44097-102 AB - The number of postsynaptic gamma-aminobutyric acid type A (GABAA) 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 GABAA receptors, through the activation of Trk B receptor tyrosine kinases. We also demonstrated that BDNF rapidly induced a sustained potentiation of GABAA 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-gamma. In addition, intracellular Ca2+ was important for the potentiation of GABAA 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 GABAA receptors in visual cortical pyramidal neurons. These results suggest that BDNF could alter the number of cell surface GABAA receptors in a region-specific manner. FAU - Mizoguchi, Yoshito AU - Mizoguchi Y AD - Cellular and Systems Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. FAU - Kanematsu, Takashi AU - Kanematsu T FAU - Hirata, Masato AU - Hirata M FAU - Nabekura, Junichi AU - Nabekura J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20030826 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (Pyridazines) RN - 0 (Receptors, GABA-A) RN - 10028-17-8 (Tritium) RN - 1400-61-9 (Nystatin) RN - 99460MG420 (gabazine) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.1.4.- (Type C Phospholipases) RN - EC 3.1.4.3 (Phospholipase C gamma) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Calcium/physiology MH - Cell Membrane/chemistry/physiology MH - Electric Conductivity MH - Enzyme Activation/drug effects MH - Enzyme Inhibitors/pharmacology MH - Nystatin MH - Patch-Clamp Techniques MH - Phospholipase C gamma MH - Pyridazines/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, trkB/metabolism MH - Receptors, GABA-A/analysis/*metabolism/physiology MH - Tritium MH - Type C Phospholipases/antagonists & inhibitors/metabolism MH - Visual Cortex/*drug effects/*metabolism/ultrastructure EDAT- 2003/08/28 05:00 MHDA- 2004/01/06 05:00 CRDT- 2003/08/28 05:00 PHST- 2003/08/28 05:00 [pubmed] PHST- 2004/01/06 05:00 [medline] PHST- 2003/08/28 05:00 [entrez] AID - S0021-9258(20)82418-1 [pii] AID - 10.1074/jbc.M305872200 [doi] PST - ppublish SO - J Biol Chem. 2003 Nov 7;278(45):44097-102. doi: 10.1074/jbc.M305872200. Epub 2003 Aug 26.