title: K(ir) and K(v) channels regulate electrical properties and proliferation of adult neural precursor cells.
abstract: The functional significance of the electrophysiological properties of neural precursor cells (NPCs) was investigated using dissociated neurosphere-derived NPCs from the forebrain subventricular zone (SVZ) of adult mice. NPCs exhibited hyperpolarized resting membrane potentials, which were depolarized by the K(+) channel inhibitor, Ba(2+). Pharmacological analysis revealed two distinct K(+) channel families: Ba(2+)-sensitive K(ir) channels and tetraethylammonium (TEA)-sensitive K(v) (primarily K(DR)) channels. Ba(2+) promoted mitogen-stimulated NPC proliferation, which was mimicked by high extracellular K(+), whereas TEA inhibited proliferation. Based on gene and protein levels in vitro, we identified K(ir)4.1, K(ir)5.1 and K(v)3.1 channels as the functional K(+) channel candidates. Expression of these K(+) channels was immunohistochemically found in NPCs of the adult mouse SVZ, but was negligible in neuroblasts. It therefore appears that expression of K(ir) and K(v) (K(DR)) channels in NPCs and related changes in the resting membrane potential could contribute to NPC proliferation and neuronal lineage commitment in the neurogenic microenvironment.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasuda
authors.forename: Perry F
authors.initials: PF
authors.lastname: Bartlett
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
mesh_terms: D000818:Animals; D001464:Barium / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051670:Shaw Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology; D000097062:Kir5.1 Channel; D000098854:Kcnj10 Channel
chemical_list: D001464:Barium; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D051670:Shaw Potassium Channels; D019789:Tetraethylammonium; D000097062:Kir5.1 Channel; D000098854:Kcnj10 Channel; C490839:Kcnc1 protein, mouse