We know that activation of protein kinase C and calcium influx are necessary and sufficient for the ability of IL-1β to depolarize rabbit synovial cells. We also know that rabbit and human cells are extensively networked via gap junctions and that the number of gap junctions is greater in tissue biopsies obtained from patients having arthritis, compared with patients who do not have the disease. We know that connexin43 is present in synovial cells, and that gap-junction intercellular communication is critical to a biological function of rabbit synovial cells, namely their ability to produce matrix metalloproteinases in response to IL-1β.
We suspect that a subtype of sodium channel is responsible for the IL-1β-induced membrane depolarization, and that the membrane currents induced by IL-1β, and possibly by other cytokines, are regulated by processes that include activation of PKC, calcium influx, and intercellular communication through gap junctions. One critically important but presently unanswered question is whether the electrophysiological changes, including changes in gap junctions, are causes or consequences of the presence of arthritis.