Interleukin-1β switches electrophysiological states of synovial fibroblasts

Abstract

The role of electrophysiological events in signal transduction of interleukin-1β (IL-1β) was investigated in rabbit synovial fibroblasts using the perforated-patch method. Aggregated synovial fibroblasts occurred in two different electrophysiological states having membrane potentials ( V m) of −63 ± 4 ( n = 71) and −27 ± 10 mV ( n = 55) (high and low V m, respectively). IL-1β affected the cells with high V m; it switched the state of the cell from high to low V m. This effect was strongly dependent on the external potential applied to the cell membrane. Low V m(−30 mV) alone without IL-1β did not switch the state of the cells. Thus a synergistic effect involving the cytokine and cell V m in switching the electrophysiological state of the cell was shown, indicating that electrophysiological changes are involved in signal transduction. Gap junctions between aggregated cells were necessary for the cells to have a high V m and to respond to IL-1β. Gap junction resistance between adjacent cells was estimated as 300 ± 100 MΩ. Our findings suggest that the electrophysiological behavior of synovial fibroblasts is tightly connected to a signaling or intracellular mediator system that is triggered by IL-1β.