TY - JOUR T1 - An Amiloride-Sensitive and Voltage-Dependent Na<sup>+</sup> Channel in an HLA-DR-Restricted Human T Cell Clone JF - The Journal of Immunology JO - J. Immunol. SP - 83 LP - 90 DO - 10.4049/jimmunol.165.1.83 VL - 165 IS - 1 AU - Lai, Zhong-Fang AU - Chen, Yu-Zhen AU - Nishimura, Yasuharu AU - Nishi, Katsuhide Y1 - 2000/07/01 UR - http://www.jimmunol.org/content/165/1/83.abstract N2 - We investigated changes in voltage-gated Na+ currents and effects of extracellular Na+ on proliferation in HLA-DR-restricted human CD4+ αβ T cells after stimulation with a non-self antigenic peptide, M12p54–68. In the absence of antigenic peptide, neither single (n = 80) nor APC-contacted (n = 71) T cells showed voltage-gated inward currents recording with whole-cell patch-clamp techniques, even with Ca2+ and Na+ ions present in the perfusion solution. However, with the same recording conditions, 31% (26 of 84) of APC-contacted T cells stimulated with the antigenic peptide showed voltage-dependent inward currents that were elicited from −60 mV. The inward currents were not inhibited in extracellular Ca2+-free conditions or in the presence of 1 mM NiCl2. However, they were completely inhibited in extracellular Na+-free conditions, which were made by replacing Na+ with iso-osmotic N-methyl-d-glucamine or choline. The Na+ currents were insensitive to tetrodotoxin, a classical blocker of Na+ channels, but were dose-dependently inhibited by amiloride, a potassium-sparing pyrazine diuretic. Furthermore, the Ag-specific proliferative response of T cells was completely inhibited in Na+-free Tyrode’s solution and was suppressed by amiloride in a dose-dependent manner. Our findings suggest that activation of amiloride-sensitive and voltage-gated Na+ channels would be an important step to allow an adequate influx of Na+ and maintain a sustained high Ca2+ level during T cell activation. ER -