Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.
Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.
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DOI：
10.1084/jem.177.3.637
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发表时间：
1993-03-01
期刊：
影响因子：
--
通讯作者：
Garcia ML
中科院分区：
文献类型：
--
作者：
Lin CS;Boltz RC;Blake JT;Nguyen M;Talento A;Fischer PA;Springer MS;Sigal NH;Slaughter RS;Garcia ML
用特异性钾通道探针研究了钾通道在人T淋巴细胞活化中的作用。Charybdotoxin（ChTX）是存在于人T细胞中的小电导Ca（2+）激活钾通道（PK，Ca）和电压门控钾通道（PK，V）的阻断剂，抑制这些细胞的活化。ChTX阻断由信号（例如，抗-CD 2、抗-CD 3、离子霉素），其通过以剂量依赖性方式防止[Ca 2 +]i升高而引起细胞内钙（[Ca 2 +] i）升高。然而，ChTX对激活途径（例如，抗-CD 28、白细胞介素2 [IL-2]），其不依赖于[Ca 2 +]i的升高。在前一种情况下，ChTX抑制增殖反应和淋巴因子（IL-2和干扰素γ）的产生。当同时加入时，或在加入刺激剂后长达4小时，可以证明ChTX的抑制作用。由于ChTX抑制PK，Ca和PK，V，我们研究了哪种通道是负责这些免疫抑制作用与使用其他两种肽，noxiustoxin（NxTX）和margatoxin（MgTX），这是具体的PK，V。这些研究表明，类似于ChTX，NxTX和MgTX抑制淋巴因子的生产和上升[Ca 2 +]i。总之，这些数据提供了证据，即PK，V的阻断通过减少T细胞活化时发生的[Ca 2 +]i升高来影响参与T淋巴细胞增殖和淋巴因子产生的Ca（2+）依赖性途径。
The role that potassium channels play in human T lymphocyte activation has been investigated by using specific potassium channel probes. Charybdotoxin (ChTX), a blocker of small conductance Ca(2+)-activated potassium channels (PK,Ca) and voltage-gated potassium channels (PK,V) that are present in human T cells, inhibits the activation of these cells. ChTX blocks T cell activation induced by signals (e.g., anti- CD2, anti-CD3, ionomycin) that elicit a rise in intracellular calcium ([Ca2+]i) by preventing the elevation of [Ca2+]i in a dose-dependent manner. However, ChTX has no effect on the activation pathways (e.g., anti-CD28, interleukin 2 [IL-2]) that are independent of a rise in [Ca2+]i. In the former case, both proliferative response and lymphokine production (IL-2 and interferon gamma) are inhibited by ChTX. The inhibitory effect of ChTX can be demonstrated when added simultaneously, or up to 4 h after the addition of the stimulants. Since ChTX inhibits both PK,Ca and PK,V, we investigated which channel is responsible for these immunosuppressive effects with the use of two other peptides, noxiustoxin (NxTX) and margatoxin (MgTX), which are specific for PK,V. These studies demonstrate that, similar to ChTX, both NxTX and MgTX inhibit lymphokine production and the rise in [Ca2+]i. Taken together, these data provide evidence that blockade of PK,V affects the Ca(2+)-dependent pathways involved in T lymphocyte proliferation and lymphokine production by diminishing the rise in [Ca2+]i that occurs upon T cell activation.
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DOI：
10.1084/jem.160.2.369
发表时间：
1984-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chandy KG;DeCoursey TE;Cahalan MD;McLaughlin C;Gupta S
通讯作者：
Gupta S
影响因子：
64.8
作者：
DECOURSEY, TE;CHANDY, KG;CAHALAN, MD
通讯作者：
CAHALAN, MD
影响因子：
11.4
作者：
STUHMER, W;RUPPERSBERG, JP;PONGS, O
通讯作者：
PONGS, O
影响因子：
56.9
作者：
CHANDY, KG;WILLIAMS, CB;GUTMAN, GA
通讯作者：
GUTMAN, GA
影响因子：
3.6
作者：
BONO, MR;SIMON, V;ROSEMBLATT, MS
通讯作者：
ROSEMBLATT, MS