Nagy P, Panyi G, Jenei A, Bene L, Gáspár R, Matkó J, Damjanovich S
Department of Biophysics, University Medical School of Debrecen, Hungary.
Immunol Lett. 1995 Jan;44(2-3):91-5. doi: 10.1016/0165-2478(94)00198-z.
Several examples have shown that plasma membrane ion channels (e.g., Ca2+ and K+ channels) make an important contribution to lymphocyte activation or thymocyte apoptosis. Here we report on the importance of these ion channels in the sensitivity or resistance of lymphoid cells to extracellular ATP-induced apoptosis. Thymocytes of Balb/c mice responded to extracellular ATP (ATPex) sensitively, with an immediate increase in the intracellular calcium level and later with an increased membrane permeability to low MW markers. Mature (medullary) thymocytes showed a higher sensitivity than did cortical thymocytes. Three human lymphoma cell lines, including SUPT13, a cell line reported to be sensitive to TcR/CD3 activation-induced apoptosis, showed a high resistance to ATPex action. These observations suggest that maturation/differentiation state-dependent activity or disappearance of early ATP-receptor operated signaling systems (including ion channels) are critical for the cells in developing towards apoptosis. Using the patch-clamp technique we demonstrated that bretylium tosylate (a particular K(+)-channel blocker) known as inhibitor of T-lymphocyte proliferation also influences the single-channel properties of voltage-gated K+ channels through depressing whole-cell K+ currents. This finding is yet another example underlying the importance of K+ channel activity in T-lymphocyte proliferation.
几个例子表明，质膜离子通道（如Ca2+和K+通道）对淋巴细胞活化或胸腺细胞凋亡起着重要作用。在此，我们报告这些离子通道在淋巴细胞对细胞外ATP诱导凋亡的敏感性或抗性中的重要性。Balb/c小鼠的胸腺细胞对细胞外ATP（ATPex）反应敏感，细胞内钙水平立即升高，随后对低分子量标记物的膜通透性增加。成熟（髓质）胸腺细胞比皮质胸腺细胞表现出更高的敏感性。三种人类淋巴瘤细胞系，包括据报道对TcR/CD3激活诱导凋亡敏感的SUPT13细胞系，对ATPex作用具有高度抗性。这些观察结果表明，早期ATP受体介导的信号系统（包括离子通道）的成熟/分化状态依赖性活性或消失对于细胞向凋亡发展至关重要。使用膜片钳技术，我们证明了已知为T淋巴细胞增殖抑制剂的甲苯磺丁脲（一种特定的K+通道阻滞剂）也通过抑制全细胞K+电流来影响电压门控K+通道的单通道特性。这一发现是K+通道活性在T淋巴细胞增殖中重要性的又一个例子。
