VOLTAGE-GATED K+ CHANNELS IN HUMAN LYMPHOCYTE-T - A ROLE IN MITOGENESIS
VOLTAGE-GATED K+ CHANNELS IN HUMAN LYMPHOCYTE-T - A ROLE IN MITOGENESIS
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DOI：
10.1038/307465a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
CAHALAN, MD
中科院分区：
文献类型：
--
作者：
DECOURSEY, TE;CHANDY, KG;CAHALAN, MD
在免疫应答中，膜受体和离子转运机制可能在淋巴细胞活化导致t淋巴细胞增殖中起重要作用。在这里，我们应用了千兆赫密封膜片钳技术1来揭示人类T淋巴细胞中离子通道的身份和特性。与神经和肌肉细胞的延迟整流相似的电压依赖性钾通道被发现是这些细胞中的主要离子通道。在整个细胞记录构象中，通道在去极化电压步骤中以s形动力学打开，最大K+电导达到3-5 nS。随后，在长时间的去极化过程中，电流几乎完全失活。通过单个K+通道的电流记录在整个细胞和外向的贴片记录构象中显示，在正常的林格溶液中，单个通道的电导约为16 pS。因此，峰值电流对应于每个电池大约200-300个传导K+通道。植物血凝素（PHA）在产生有丝分裂的浓度下，在加入洗浴液1分钟内改变K+通道门控制，导致通道更快地打开，并以更负的膜电位打开。在PHA刺激后，T淋巴细胞的3h -胸苷结合可被“经典”K+通道阻滞剂四乙基铵和4-氨基吡啶以及奎宁所抑制，奎宁的剂量可阻断电压压制T淋巴细胞中的K+通道，这表明K+通道可能在有丝分裂发生中起作用。
Membrane receptors and ion transport mechanisms probably have an important role in lymphocyte activation leading to T-lymphocyte proliferation in the immune response. Here we have applied a gigaohm-seal patch clamp technique1to reveal the identity and properties of ion channels in human T lymphocytes. A voltage-dependent potassium channel bearing a resemblance to the delayed rectifier of nerve and muscle cells was found to be the predominant ion channel in these cells. In the whole cell recording conformation, the channels open with sigmoid kinetics during depolarizing voltage steps, reaching a maximum K+conductance of 3–5 nS. The current subsequently becomes almost completely inactivated during a long-lasting depolarization. Currents through single K+channels recorded in whole cell and outside-out patch recording conformations reveal a unitary channel conductance of about 16 pS in normal Ringer solution. Thus, the peak current corresponds to approximately 200–300 conducting K+channels per cell. Phytohaemag-glutinin (PHA), at concentrations that produce mitogenesis, alters K+channel gating within 1 min of addition to the bathing solution, causing channels to open more rapidly and at more negative membrane potentials.3H-thymidine incorporation by T lymphocytes following PHA stimulation is inhibited by the ‘classical’ K+channel blockers tetraethylammonium and 4-aminopyridine, and also by quinine, at doses found to block the K+channel in voltage-clamped T lymphocytes, suggesting that K+channels may play a part in mitogenesis.