Physiological significance of delayed rectifier K+ channels (Kv1.3) expressed in T lymphocytes and their pathological significance in chronic kidney disease

Abstract

T lymphocytes predominantly express delayed rectifier K+ channels (Kv1.3) in their plasma membranes. More than 30 years ago, patch-clamp studies revealed that the channels play crucial roles in facilitating the calcium influx necessary to trigger lymphocyte activation and proliferation. In addition to selective channel inhibitors that have been developed, we recently showed physiological evidence that drugs such as nonsteroidal anti-inflammatory drugs, antibiotics, and anti-hypertensives effectively suppress the channel currents in lymphocytes, and thus exert immunosuppressive effects. Using experimental animal models, previous studies revealed the pathological relevance between the expression of ion channels and the progression of renal diseases. As an extension, we recently demonstrated that the overexpression of lymphocyte Kv1.3 channels contributed to the progression of chronic kidney disease (CKD) by promoting cellular proliferation and interstitial fibrosis. Together with our in-vitro results, the studies indicated the therapeutic potency of Kv1.3-channel inhibitors in the treatment or the prevention of CKD.