title: Activation of calcium-dependent potassium channels in mouse [correction of rat] brain neurons by neurotrophin-3 and nerve growth factor.
abstract: The neurotrophins are signaling factors that are essential for survival and differentiation of distinct neuronal populations during the development and regeneration of the nervous system. The long-term effects of neurotrophins have been studied in detail, but little is known about their acute effects on neuronal activity. Here we use permeabilized whole-cell patch clamp to demonstrate that neurotrophin-3 (NT-3) and nerve growth factor activate calcium-dependent, paxilline-sensitive potassium channels (BK channels) in cortical neurons. Application of NT-3 or nerve growth factor produced a rapid and gradual rise in BK current that was sustained for 30-50 min; brain-derived neurotrophic factor, ciliary neurotrophic factor, and insulin-like growth factor-1 had no significant effect. The response to NT-3 was blocked by inhibitors of protein kinases, phospholipase C, and serine/threonine protein phosphatase 1 and 2a. Omission of Ca2+ from the extracellular medium prevented the NT-3 effect. Our results indicate that NT-3 stimulates BK channel activity in cortical neurons through a signaling pathway that involves Trk tyrosine kinase, phospholipase C, and protein dephosphorylation and is calcium-dependent. Activation of BK channels may be a major mechanism by which neurotrophins acutely regulate neuronal activity.
authors.affiliation: NeuroSearch, Glostrup, Denmark.
authors.forename: N R
authors.initials: NR
authors.lastname: Holm
authors.forename: P
authors.initials: P
authors.lastname: Christophersen
authors.forename: S P
authors.initials: SP
authors.lastname: Olesen
authors.forename: S
authors.initials: S
authors.lastname: Gammeltoft
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology*; D020933:Neurotrophin 3; D019319:Okadaic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D054645:Protein Phosphatase 1; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction
chemical_list: D004791:Enzyme Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D019319:Okadaic Acid; D011505:Protein-Tyrosine Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D002118:Calcium