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Background: The Kv 1.3 potassium channel serves as an important regulator of lymphocyte function.Blockade of the channel depolarizes the cell membrane and attenuates the Ca2+ signaling pathway that is crucial for lymphocyte activation.Diphenyl phosphine oxide-1 (DPO-1) is a novel and potent inhibitor of Kvl.5 potassium channel that is hoped to be used in the clinical therapy of atrial fibrillation (AF).Objective: To investigate the effect of DPO-1 on Kv1.3 potassium channel and I1-2 secretion.Methods: The whole-cell patch-clamp technique was applied to record potassium currents.The expression of Kv 1.3 channel gene was detected by Real-time PCR.Intracellular calcium was mesured using fluo-3.IL-2 production was measured with an ELISA kit.Results: DPO-1 inhibited the Kv 1.3 channel current in a concentration-dependent with IC50 =3.10±0.41pM at +40mV.The drug binds to the open state ofKv1.3 channel preferentially.Pretreatment of Jurkat T cells for 24 h with 3 and 10 pM DPO-1 led to significant reduced Kvl.3 mRNA expression.Calcium fluoresecence measurement showed that the influx Ca2+ to Ca2+-depleted cells was significant blunted by 24 h pretreatment with DPO-1 (1 and 3 μM).IL-2 production in actived Jurkat T-lymphocytes were significant reduced by 3 and 10μM DPO-1.Conclusion: Our results suggested that DPO-1 may also have a potent immunomodulatory role and relieve the inflammation, which might additionally benefit for AF therapy.