title: Spontaneous calcium transients in human neural progenitor cells mediated by transient receptor potential channels.
abstract: Calcium signals affect many developmental processes, including proliferation, migration, survival, and apoptosis, processes that are of particular importance in stem cells intended for cell replacement therapies. The mechanisms underlying Ca(2+) signals, therefore, have a role in determining how stem cells respond to their environment, and how these responses might be controlled in vitro. In this study, we examined the spontaneous Ca(2+) activity in human neural progenitor cells during proliferation and differentiation. Pharmacological characterization indicates that in proliferating cells, most activity is the result of transient receptor potential (TRP) channels that are sensitive to Gd(3+) and La(3+), with the more subtype selective antagonist Ruthenium red also reducing activity, suggesting the involvement of transient receptor potential vanilloid (TRPV) channels. In differentiating cells, Gd(3+) and La(3+)-sensitive TRP channels also appear to underlie the spontaneous activity; however, no sub-type-specific antagonists had any effect. Protein levels of TRPV2 and TRPV3 decreased in differentiated cells, which is demonstrated by western blot. Thus, it appears that TRP channels represent the main route of Ca(2+) entry in human neural progenitor cells (hNPCs), but the responsible channel types are subject to substitution under differentiating conditions. The level of spontaneous activity could be increased and decreased by lowering and raising the extracellular K(+) concentration. Proliferating cells in low K(+) slowed the cell cycle, with a disproportionate increased percentage of cells in G1 phase and a reduction in S phase. Taken together, these results suggest a link between external K(+) concentration, spontaneous Ca(2+) transients, and cell cycle distribution, which is able to influence the fate of stem and progenitor cells.
authors: University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration, Rostock, Germany.
authors: Peter J
authors: PJ
authors: Morgan
authors: Rayk
authors: R
authors: Hübner
authors: Arndt
authors: A
authors: Rolfs
authors: Moritz J
authors: MJ
authors: Frech
mesh_terms: D015220:Calcium Channels / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D005682:Gadolinium / Q000737:chemistry; D006801:Humans; D058953:Neural Stem Cells / Q000737:chemistry / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C400769:TRPV2 protein, human; C459445:TRPV3 protein, human; D012430:Ruthenium Red; D005682:Gadolinium; D011188:Potassium