0 23 Charybdotoxin-sensitive charybdotoxin-sensitive JJ 23 24 , , , 25 41 Ca(2+)-dependent ca(2+)-dependent JJ 42 50 membrane membrane NN 51 60 potential potential NN 61 68 changes change NNS 69 72 are be VBP 73 76 not not RB 77 85 involved involve VBN 86 88 in in IN 89 94 human human JJ 95 96 T t NN 97 99 or or CC 100 101 B B NNP 102 106 cell cell NN 107 117 activation activation NN 118 121 and and CC 122 135 proliferation proliferation NN 135 136 . . . 138 141 The the DT 142 153 involvement involvement NN 154 156 of of IN 157 160 ion ion NN 161 169 channels channel NNS 170 172 in in IN 173 174 B B NNP 175 178 and and CC 179 180 T t NN 181 191 lymphocyte lymphocyte NN 192 202 activation activation NN 203 205 is be VBZ 206 215 supported support VBN 216 218 by by IN 219 223 many many JJ 224 231 reports report NNS 232 234 of of IN 235 242 changes change NNS 243 245 in in IN 246 249 ion ion NN 250 256 fluxes flux NNS 257 260 and and CC 261 269 membrane membrane NN 270 279 potential potential NN 280 285 after after IN 286 293 mitogen mitogen NN 294 301 binding binding NN 301 302 . . . 303 308 Human human JJ 309 310 T t NN 311 314 and and CC 315 316 B b NN 317 328 lymphocytes lymphocyte NNS 329 340 demonstrate demonstrate VBP 341 343 an an DT 344 349 early early JJ 350 353 and and CC 354 363 transient transient JJ 364 381 hyperpolarization hyperpolarization NN 382 387 after after IN 388 394 ligand ligand NN 395 402 binding binding NN 402 403 . . . 404 412 Inasmuch inasmuch RB 413 415 as as IN 416 419 the the DT 420 426 change change NN 427 429 in in IN 430 438 membrane membrane NN 439 448 potential potential NN 449 451 is be VBZ 452 461 dependent dependent JJ 462 464 on on IN 465 474 elevation elevation NN 475 477 of of IN 478 482 free free JJ 483 492 cytosolic cytosolic JJ 493 500 calcium calcium NN 500 501 , , , 502 505 the the DT 506 523 hyperpolarization hyperpolarization NN 524 526 is be VBZ 527 537 presumably presumably RB 538 545 through through IN 546 553 opening opening NN 554 556 of of IN 557 574 Ca(2+)-stimulated ca(2+)-stimulated JJ 575 577 K+ k+ NN 578 586 channels channel NNS 586 587 . . . 588 590 We we PRP 591 595 have have VBP 596 600 used use VBN 601 614 charybdotoxin charybdotoxin NN 614 615 , , , 616 617 a a DT 618 623 known known JJ 624 633 inhibitor inhibitor NN 634 636 of of IN 637 653 Ca(2+)-dependent ca(2+)-dependent JJ 654 656 K+ K+ NNP 657 665 channels channel NNS 665 666 , , , 667 669 to to TO 670 675 study study VB 676 679 the the DT 680 684 role role NN 685 687 of of IN 688 693 these these DT 694 702 channels channel NNS 703 705 in in IN 706 716 lymphocyte lymphocyte NN 717 727 activation activation NN 728 731 and and CC 732 743 mitogenesis mitogenesis NN 743 744 . . . 745 747 We we PRP 748 759 demonstrate demonstrate VBP 760 764 that that IN 765 778 charybdotoxin charybdotoxin NN 779 787 inhibits inhibit VBZ 788 791 the the DT 792 806 ligand-induced ligand-induced JJ 807 816 transient transient JJ 817 825 membrane membrane NN 826 843 hyperpolarization hyperpolarization NN 844 846 in in IN 847 848 B B NNP 849 852 and and CC 853 854 T t NN 855 860 cells cell NNS 861 863 in in IN 864 865 a a DT 866 880 dose-dependent dose-dependent JJ 881 888 fashion fashion NN 888 889 , , , 890 897 without without IN 898 907 affecting affect VBG 908 915 changes change NNS 916 918 in in IN 919 928 cytosolic cytosolic JJ 929 933 Ca2+ ca2+ NN 933 934 . . . 935 942 However however RB 942 943 , , , 944 952 blockade blockade NN 953 955 of of IN 956 959 the the DT 960 976 Ca(2+)-activated ca(2+)-activated JJ 977 979 K+ k+ NN 980 987 channel channel NN 988 990 is be VBZ 991 994 not not RB 995 1005 associated associate VBN 1006 1010 with with IN 1011 1018 changes change NNS 1019 1021 in in IN 1022 1032 cell-cycle cell-cycle NN 1033 1037 gene gene NN 1038 1048 activation activation NN 1048 1049 , , , 1050 1054 IL-2 il-2 NN 1055 1065 production production NN 1065 1066 , , , 1067 1072 IL-2R IL-2R NNP 1073 1083 expression expression NN 1084 1086 or or CC 1087 1088 B B NNP 1089 1092 and and CC 1093 1094 T t NN 1095 1099 cell cell NN 1100 1111 mitogenesis mitogenesis NN 1111 1112 . . . 1113 1118 These these DT 1119 1126 results result NNS 1127 1132 imply imply VBP 1133 1137 that that IN 1138 1146 membrane membrane NN 1147 1156 potential potential NN 1157 1164 changes change NNS 1165 1174 secondary secondary JJ 1175 1177 to to TO 1178 1181 the the DT 1182 1198 ligand-dependent ligand-dependent JJ 1199 1206 opening opening NN 1207 1209 of of IN 1210 1226 Ca(2+)-activated ca(2+)-activated JJ 1227 1229 K+ k+ NN 1230 1238 channels channel NNS 1239 1242 are be VBP 1243 1246 not not RB 1247 1255 involved involve VBN 1256 1258 in in IN 1259 1260 B B NNP 1261 1264 and and CC 1265 1266 T t NN 1267 1277 lymphocyte lymphocyte NN 1278 1288 activation activation NN 1289 1292 and and CC 1293 1304 mitogenesis mitogenesis NN 1304 1305 . . .