Differential mechanisms of margatoxin- and quercetin-induced regulation of voltage-gated ion currents in Jurkat T lymphocytes.

Margatoxin and quercetin can have an immunomodulatory role in T lymphocytes. It remains to be further investigated how these substances affect ion currents in T lymphocytes. With the aid of whole-cell patch-clamp technique, we assessed the effect of margatoxin on ion currents in Jurkat T lymphocytes. Whole-cell K+ outward currents (IK) with an outward rectification found in these cells were identified as the Kv1.3 current. We also found out that unlike iberiotoxin or charybdotoxin, margatoxin could be effective in blocking the amplitude of IK in a concentration-dependent manner, although its IC50 value was slightly higher as compared with previous reports. Similar results were also obtained in the presence of agitoxin. Unlike verapamil and quercetin, margatoxin block IK in a time-independent manner. No effect of margatoxin on L-type Ca2+ current in Jurkat T lymphocytes was found, although quercetin (10 µM) enhanced it. In addition, no effects of this toxin (up to 10 µM) on the activity of large-conductance Ca2+-activated K+ channels in pituitary GH3 cells and in human skeletal muscle cells were demonstrated. In intracellular Ca2+ measurements, pretreatment of Fura-2-loaded Jurkat T lymphocytes with margatoxin was also found to attenuate the ionomycin-induced increase in intracellular Ca2+. Our results indicate that margatoxin and quercetin may differentially influence ion currents in T lymphocytes. [ABSTRACT FROM AUTHOR]