CYCLING WERNERS-SYNDROME FIBROBLASTS DISPLAY CALCIUM-DEPENDENT POTASSIUM CURRENTS

Werner's Syndrome (WS) fibroblasts undergo premature senescence. Two h ypotheses have been proposed to explain this phenomenon: (i) the pheno type is due to the overexpression of senescence-specific proteins in e very cell in the population, Such proteins are known to suppress calci um-dependent potassium currents. (ii) The WS mutation greatly increase s the proportion of cells that stop cycling at each generation and bec ome senescent. If hypothesis (i) is correct, such currents should be s uppressed in all WS fibroblasts; whereas hypothesis (ii) predicts that they will be retained in the cycling fraction of the population. To d istinguish between these hypotheses whole-cell patch-clamp currents we re recorded from cycling cells. Slowly activating outward calcium-depe ndent potassium currents were detected in both cycling WS and control fibroblasts. These findings support hypothesis (ii): the premature sen escence of WS fibroblasts is due to an increased rate of transition fr om cycling to senescence in the total cell population. (C) 1997 Academ ic Press.