SUPPRESSION OF CALCIUM-DEPENDENT MEMBRANE CURRENTS IN HUMAN FIBROBLASTS BY REPLICATIVE SENESCENCE AND FORCED EXPRESSION OF A GENE SEQUENCE ENCODING A PUTATIVE CALCIUM-BINDING PROTEIN

Human diploid fibroblasts (HDFs) possess Ca2+-dependent membrane curre nts. These currents were suppressed in late-passage normal (senescent) HDFs and prematurely senescent HDFs derived from a subject with Werne r syndrome (WS), compared with early-passage normal (young) HDFs. When young HDFs were microinjected with mRNA transcribed in vitro from a c DNA (WS3-10) which encodes a protein bearing a putative Ca2+-binding s ite and whose endogenous gene is overexpressed in senescent and WS HDF s, membrane currents fell to levels present in senescent and WS HDFs. Thus, both replicative senescence and forced expression of the WS3-10 gene sequence lead to suppression of Ca2+-dependent membrane currents, which suggests that a causal connection exists between these two proc esses.