title: Moderate hypoxia influences potassium outward currents in adipose-derived stem cells.
abstract: Moderate hypoxic preconditioning of adipose-derived stem cells (ASCs) enhances properties such as proliferation and secretion of growth factors, representing a valuable strategy to increase the efficiency of cell-based therapies. In a wide variety of cells potassium (K+) channels are key elements involved in the cellular responses to hypoxia, suggesting that ASCs cultured under low oxygen conditions may display altered electrophysiological properties. Here, the effects of moderate hypoxic culture on proliferation, whole-cell currents, and ion channel expression were investigated using human ASCs cultured at 5% and 20% oxygen. Although cell proliferation was greatly enhanced, the dose-dependent growth inhibition by the K+ channel blocker tetraethylammonium (TEA) was not significantly affected by hypoxia. Under both normoxic and hypoxic conditions, ASCs displayed outward K+ currents composed by Ca2+-activated, delayed rectifier, and transient components. Hypoxic culture reduced the slope of the current-voltage curves and caused a negative shift in the voltage activation threshold of the whole-cell currents. However, the TEA-mediated shift of voltage activation threshold was not affected by hypoxia. Semiquantitative real-time RT-PCR revealed that expression of genes encoding for various ion channels subunits related to oxygen sensing and proliferation remained unchanged after hypoxic culture. In conclusion, outward currents are influenced by moderate hypoxia in ASCs through a mechanism that is not likely the result of modulation of TEA-sensitive K+ channels.
authors.affiliation: Laboratory for Stem Cell Research, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Mayuri
authors.initials: M
authors.lastname: Prasad
authors.affiliation: Laboratory for Stem Cell Research, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zachar
authors.affiliation: Laboratory for Stem Cell Research, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Fink
authors.affiliation: Laboratory for Stem Cell Research, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Cristian Pablo
authors.initials: CP
authors.lastname: Pennisi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism*; D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D019789:Tetraethylammonium