Gelfand E W, Or R
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
J Immunol. 1991 Nov 15;147(10):3452-8.
The involvement of ion channels in B and T lymphocyte activation is supported by many reports of changes in ion fluxes and membrane potential after mitogen binding. Human T and B lymphocytes demonstrate an early and transient hyperpolarization after ligand binding. Inasmuch as the change in membrane potential is dependent on elevation of free cytosolic calcium, the hyperpolarization is presumably through opening of Ca(2+)-stimulated K+ channels. We have used charybdotoxin, a known inhibitor of Ca(2+)-dependent K+ channels, to study the role of these channels in lymphocyte activation and mitogenesis. We demonstrate that charybdotoxin inhibits the ligand-induced transient membrane hyperpolarization in B and T cells in a dose-dependent fashion, without affecting changes in cytosolic Ca2+. However, blockade of the Ca(2+)-activated K+ channel is not associated with changes in cell-cycle gene activation, IL-2 production, IL-2R expression or B and T cell mitogenesis. These results imply that membrane potential changes secondary to the ligand-dependent opening of Ca(2+)-activated K+ channels are not involved in B and T lymphocyte activation and mitogenesis.
许多关于有丝分裂原结合后离子通量和膜电位变化的报道支持了离子通道参与B和T淋巴细胞激活的观点。人T和B淋巴细胞在配体结合后表现出早期短暂的超极化。由于膜电位的变化依赖于胞质游离钙的升高，推测这种超极化是通过钙激活钾通道的开放实现的。我们使用了已知的钙依赖性钾通道抑制剂蝎毒素，来研究这些通道在淋巴细胞激活和有丝分裂中的作用。我们证明，蝎毒素以剂量依赖的方式抑制B细胞和T细胞中配体诱导的短暂膜超极化，而不影响胞质Ca2+的变化。然而，钙激活钾通道的阻断与细胞周期基因激活、IL-2产生、IL-2R表达或B细胞和T细胞有丝分裂的变化无关。这些结果表明，钙激活钾通道配体依赖性开放继发的膜电位变化不参与B和T淋巴细胞激活和有丝分裂。
