title: Cycling Werner's syndrome fibroblasts display calcium-dependent potassium currents.
abstract: Werner's Syndrome (WS) fibroblasts undergo premature senescence. Two hypotheses have been proposed to explain this phenomenon: (i) the phenotype is due to the overexpression of senescence-specific proteins in every cell in the population. Such proteins are known to suppress calcium-dependent potassium currents. (ii) The WS mutation greatly increases the proportion of cells that stop cycling at each generation and become senescent. If hypothesis (i) is correct, such currents should be suppressed in all WS fibroblasts; whereas hypothesis (ii) predicts that they will be retained in the cycling fraction of the population. To distinguish between these hypotheses whole-cell patch-clamp currents were recorded from cycling cells. Slowly activating outward calcium-dependent potassium currents were detected in both cycling WS and control fibroblasts. These findings support hypothesis (ii): the premature senescence of WS fibroblasts is due to an increased rate of transition from cycling to senescence in the total cell population.
authors.affiliation: Department of Pharmacy, University of Brighton, Brighton, BN2 4GJ, United Kingdom.
authors.forename: R G
authors.initials: RG
authors.lastname: Faragher
authors.forename: S P
authors.initials: SP
authors.lastname: Hardy
authors.forename: T
authors.initials: T
authors.lastname: Davis
authors.forename: S
authors.initials: S
authors.lastname: Dropcova
authors.forename: M C
authors.initials: MC
authors.lastname: Allen
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D016922:Cellular Senescence; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D008840:Microfilament Proteins; D009124:Muscle Proteins / Q000235:genetics; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; D015221:Potassium Channels; C058992:Tagln protein, mouse; C051615:transgelin; D011188:Potassium; D002118:Calcium