PMID- 12405954 OWN - NLM STAT- MEDLINE DCOM- 20030108 LR - 20190815 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 16 IP - 8 DP - 2002 Oct TI - Brain-derived neurotrophic factor induces long-lasting Ca2+-activated K+ currents in rat visual cortex neurons. PG - 1417-24 AB - Brain-derived neurotrophic factor (BDNF) increases postsynaptic intracellular Ca2+ and modulates synaptic transmission in various types of neurons. Ca2+-activated K+ currents, opened mainly by intracellular Ca2+ elevation, contribute to hyperpolarization following action potentials and modulate synaptic transmission. We asked whether BDNF induces Ca2+-activated K+ currents by postsynaptic elevation of intracellular Ca2+ in acutely dissociated visual cortex neurons of rats. Currents were analysed using the nystatin-perforated patch clamp technique and imaging of intracellular Ca2+ mobilization with fura-2. At a holding potential of -50 mV, BDNF application (20 ng/mL) for 1-2 min induced an outward current (IBDNF-OUT; 80.0 +/- 29.0 pA) lasting for more than 90 min without attenuation in every neuron tested. K252a (200 nm), an inhibitor of Trk receptor tyrosine kinase, and U73122 (3 microm), a specific phospholipase C (PLC)-gamma inhibitor, suppressed IBDNF-OUT completely. IBDNF-OUT was both charybdotoxin- (600 nm) and apamin- (300 nm) sensitive, suggesting that this current was carried by Ca2+-activated K+ channels. BAPTA-AM (150 microm) gradually suppressed IBDNF-OUT. Fura-2 imaging revealed that a brief application of BDNF elicited a long-lasting elevation of intracellular Ca2+. These results show that BDNF induces long-lasting Ca2+-activated K+ currents by sustained intracellular Ca2+ elevation in rat visual cortex neurons. While BDNF, likely acting through the Trk B receptor, was necessary for the induction of long-lasting Ca2+-activated K+ currents via intracellular Ca2+ elevation, BDNF was not necessary for the maintenance of this current. FAU - Mizoguchi, Yoshito AU - Mizoguchi Y AD - Department of Cellular and Systems Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. FAU - Monji, Akira AU - Monji A FAU - Nabekura, Junichi AU - Nabekura J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Isoenzymes) RN - 0 (Potassium Channel Blockers) RN - 0 (Potassium Channels, Calcium-Activated) 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 - Action Potentials/drug effects/*physiology MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology MH - Calcium/metabolism MH - Calcium Signaling/drug effects/*physiology MH - Cell Membrane/drug effects/metabolism MH - Cells, Cultured MH - Intracellular Fluid/drug effects/metabolism MH - Isoenzymes/drug effects/metabolism MH - Membrane Potentials/drug effects/physiology MH - Neurons/cytology/drug effects/*metabolism MH - Phospholipase C gamma MH - Phosphorylation/drug effects MH - Potassium Channel Blockers/pharmacology MH - Potassium Channels, Calcium-Activated/drug effects/*metabolism MH - Rats MH - Rats, Wistar MH - Receptor, trkB/drug effects/metabolism MH - Synaptic Transmission/drug effects/*physiology MH - Type C Phospholipases/drug effects/metabolism MH - Visual Cortex/cytology/drug effects/*metabolism EDAT- 2002/10/31 04:00 MHDA- 2003/01/09 04:00 CRDT- 2002/10/31 04:00 PHST- 2002/10/31 04:00 [pubmed] PHST- 2003/01/09 04:00 [medline] PHST- 2002/10/31 04:00 [entrez] AID - 2198 [pii] AID - 10.1046/j.1460-9568.2002.02198.x [doi] PST - ppublish SO - Eur J Neurosci. 2002 Oct;16(8):1417-24. doi: 10.1046/j.1460-9568.2002.02198.x.