An intermediate-conductance Ca2+-activated K+ channel mediates B lymphoma cell cycle progression induced by serum
An intermediate-conductance Ca2+-activated K+ channel mediates B lymphoma cell cycle progression induced by serum
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DOI：
10.1007/s00424-007-0258-7
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发表时间：
2007-09-01
影响因子：
4.5
通讯作者：
Ma, He-Ping
中科院分区：
文献类型：
--
作者：
Wang, Jing;Xu, Yu-Qing;Ma, He-Ping
我们之前报道过Kv1.3通道在Daudi细胞中表达。然而，本研究表明，Daudi 细胞周期进程不受 Margatoxin（一种 Kv1.3 通道阻断剂）的影响，但可以被四乙铵 (TEA) 和 1-[(2-氯苯基)二苯甲基]-1H-吡唑 (TRAM-34)（一种中等电导 Ca2+ 激活的 K+ (IK) 通道的选择性阻断剂）抑制。我们的膜片钳数据表明 Daudi 细胞表达 IK 通道，因为它的单位电导约为 30 pS，与电压无关，并且可以被亚微摩尔 Ca2+ 激活并被 TRAM-34 阻断。胎牛血清 (FBS) 升高细胞内 Ca2+ 浓度 ([Ca2+](i)) 并激活该 IK 通道。相反，Rituximab（一种 CD20 的人-鼠嵌合单克隆抗体）显着降低 [Ca2+](i) 并抑制通道。此外，用磷脂酰肌醇 3 激酶 (PI3K) 抑制剂 LY-294002 治疗可减弱 FBS 诱导的 IK 通道表达和细胞周期进程。这些数据共同表明，FBS 中的生长因子通过 CD20 提高 IK 通道活性和通过 PI3K 提高细胞表面的 IK 通道表达来触发细胞周期进程。因此，IK 通道活性和表达升高可能部分解释了 Daudi 细胞的恶性生长和增殖。
We have previously reported that Kv1.3 channel is expressed in Daudi cells. However, the present study demonstrates that Daudi cell cycle progression is not affected by margatoxin, a Kv1.3 channel blocker, but can be suppressed by tetraethylammonium (TEA) and 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34), a selective blocker of intermediate-conductance Ca2+-activated K+ (IK) channels. Our patch-clamp data indicate that Daudi cells express an IK channel because it has a unit conductance of about 30 pS, is voltage-independent, and can be activated by submicromolar Ca2+ and blocked by TRAM-34. Fetal bovine serum (FBS) elevated intracellular Ca2+ concentration ([Ca2+](i)) and activated this IK channel. Conversely, Rituximab, a human-mouse chimeric monoclonal antibody of CD20, significantly decreased [Ca2+](i) and inhibited the channel. Furthermore, both FBS-induced IK channel expression and cell cycle progression were attenuated by the treatment with LY-294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. These data together suggest that a growth factor(s) in FBS triggers cell cycle progression by elevating both IK channel activity via CD20 and IK channel expression on the cell surface via PI3K. Thus, elevated IK channel activity and expression may account, in part, for Daudi cell malignant growth and proliferation.