Interleukin-1 beta switches electrophysiological states of synovial fibroblasts

The role of electrophysiological events in signal transduction of interleukin-1 beta (IL-1 beta) 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-1 beta 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-1 beta 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-1 beta. Gap junction resistance between adjacent cells was estimated as 300 +/- 100 M Omega. 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-1 beta.