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

Thapsigargin has been shown the elevate intracellular Na+ concentration in human lymphocytes, but mechanisms underlying thapsigargin-induced Na+ entry are little understood. In the present study we investigated thapsigargin-induced changes in cytosolic free Na+ and Ca2+ concentration in human lymphocytes after inhibition of the Na+/Ca2+ exchange with two structurally unrelated compounds, dimethylthiourea ad bepridil. The intracellular Na+ increase induced by 5 µM thapsigargin was significantly enhanced in the presence of 5 mM dimethylthiourea or 40 µM bepridil. In contrast, both compounds significantly decreased the thapsigargin-induced intracellular Ca2+ elevation. No effect of dimethylthiourea or bepridil on thapsigargin-induced Ca2+ influx was observed in the absence of extracellular Na+. These observations are consistent with the hypothesis that thapsigargin stimulates Na+/Ca2+ exchange in human lymphocytes. However, Na+/Ca2+ exchange does not mediate Na+ influx in human lymphocytes.