Na+/Ca2+ exchange inhibitors modulate thapsigargin-induced Ca2+ and Na+ influx in human lymphocytes

Thapsigargin has been shown the elevate intracellular Naf concentration in human lymphocytes, but mechanisms underlying thapsigargin-induced Na+ entry are little understood. In the present study we investigated thapsigargin-i nduced changes in cytosolic free Na+ and Ca2+ concentration in human lympho cytes after inhibition of the Na+/Ca2+ exchange with two structurally unrel ated compounds, dimethylthiourea ad bepridil. The intracellular Naf increas e induced by 5 mu M thapsigargin was significantly enhanced in the presence of 5 mM dimethylthiourea or 40 mu M bepridil. In contrast, both compounds significantly decreased the thapsigargin-induced intracellular Ca2+ elevati on. No effect of dimethylthiourea or bepridil on thapsigargin-induced Ca2influx was observed in the absence of extracellular Na+. These observations are consistent with the hypothesis that thapsigargin stimulates Na+/Ca2+ e xchange in human lymphocytes. However, Na+/Ca2+ exchange does not mediate N a+ influx in human lymphocytes.