title: KCa3.1 modulates neuroblast migration along the rostral migratory stream (RMS) in vivo.
abstract: From the subventricular zone (SVZ), neuronal precursor cells (NPCs), called neuroblasts, migrate through the rostral migratory stream (RMS) to become interneurons in the olfactory bulb (OB). Ion channels regulate neuronal migration during development, yet their role in migration through the adult RMS is unknown. To address this question, we utilized Nestin-CreER(T2)/R26R-YFP mice to fluorescently label neuroblasts in the adult. Patch-clamp recordings from neuroblasts reveal K(+) currents that are sensitive to intracellular Ca(2+) levels and blocked by clotrimazole and TRAM-34, inhibitors of intermediate conductance Ca(2+)-activated K(+) (KCa3.1) channels. Immunolabeling and electrophysiology show KCa3.1 expression restricted to neuroblasts in the SVZ and RMS, but absent in OB neurons. Time-lapse confocal microscopy in situ showed inhibiting KCa3.1 prolonged the stationary phase of neuroblasts' saltatory migration, reducing migration speed by over 50%. Both migration and KCa3.1 currents could also be inhibited by blocking Ca(2+) influx via transient receptor potential (TRP) channels, which, together with positive immunostaining for transient receptor potential canonical 1 (TRPC1), suggest that TRP channels are an important Ca(2+) source modulating KCa3.1 activity. Finally, injecting TRAM-34 into Nestin-CreER(T2)/R26R-YFP mice significantly reduced the number of neuroblasts that reached the OB, suggesting an important role for KCa3.1 in vivo. These studies describe a previously unrecognized protein in migration of adult NPCs.
authors.affiliation: Department of Neurobiology and Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Turner
authors.affiliation: Department of Neurobiology and Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Harald
authors.initials: H
authors.lastname: Sontheimer
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002491:Central Nervous System Agents / Q000494:pharmacology; D003022:Clotrimazole / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D002491:Central Nervous System Agents; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496925:Kcnn4 protein, mouse; D011720:Pyrazoles; C411671:TRAM 34; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D003022:Clotrimazole; D011188:Potassium; D002118:Calcium
keywords: KCa channels; KCa3.1; TRP channels; migration; rostral migratory stream