K channels are expressed early in human T-cell development.
K channels are expressed early in human T-cell development.
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K 通道在人类 T 细胞发育早期表达。
DOI：
10.1073/pnas.83.15.5625
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发表时间：
1986
影响因子：
11.1
通讯作者：
Hagiwara,S
中科院分区：
文献类型：
--
作者：
Schlichter,L;Sidell,N;Hagiwara,S
成熟的人T淋巴细胞对有丝分裂原植物血凝素（PHA）有增殖反应，但缺乏T3受体的未成熟胸腺细胞（T3-胸腺细胞）没有增殖反应。由于成熟T细胞的增殖需要功能性的K通道，我们询问免疫功能不全的T3胸腺细胞是否缺乏正常的K通道。我们报道T3胸腺细胞具有与成熟外周T细胞相似的K+电流，即相似的电压依赖性、激活和失活动力学以及药理学。此外，两种细胞类型的最大特定K+电导是相同的，这意味着每个细胞中可激活通道的密度相似。在评估通道对PHA的功能反应时，我们发现未成熟细胞和成熟细胞的K+电流对有丝分裂原的反应相似。激活K+电流的阈值电压附近的响应是可变的；经PHA处理后，K+电导和活化率分别升高、降低或保持不变。对于一些电池，电导和激活动力学的电压依赖性在相反的方向上移动。在更高的正电压下，PHA持续导致10-20%的电导抑制，这不是由于增加了向内电流，激活或失活的时间过程发生了变化，也不是由于失活的稳态水平发生了变化。PHA对K+电流的影响不能简单地用表面电位的变化来解释，而表面电位的变化被认为是触发t细胞增殖的原因。综上所述，我们的研究结果表明，K通道在T细胞分化过程中很早就表达了，可能在胸腺加工之前，K+电流对PHA的差异反应不能解释T3-胸腺细胞增殖失败的原因，表面电位的变化可能不是PHA激活T细胞的必要早期事件。
Mature human T lymphocytes proliferate in response to the mitogen phytohemagglutinin (PHA), but immature thymocytes lacking the T3 receptor (T3- thymocytes) do not. Because functioning K channels are required for proliferation of mature T cells, we asked whether immunoincompetent T3- thymocytes lack normal K channels. We report that T3- thymocytes have a K+ current similar to that of mature peripheral T cells--that is, similar voltage dependence, activation and inactivation kinetics, and pharmacology. Moreover, the maximal specific K+ conductance is the same for both cell types, implying a similar density of activable channels in each cell. In assessing the functional responses of the channels to PHA, we found that the K+ current of immature and mature cells responds similarly to the mitogen. Responses near the threshold voltage for activating the K+ current were variable; the K+ conductance and rate of activation were increased, decreased, or unchanged after PHA treatment. For several cells, the voltage dependence of the conductance and activation kinetics was shifted in opposite directions. At more positive voltages, PHA consistently caused a 10-20% suppression of conductance that was not due to the addition of an inward current, to changes in the time course of activation or inactivation, or to changes in the steady-state level of inactivation. The effects of PHA on the K+ current cannot be explained by a simple shift in surface potential, as has been hypothesized to be involved in its triggering of T-cell proliferation. Taken together, our findings show K channels are expressed very early in T-cell differentiation, possibly before thymic processing, differential responses of the K+ current to PHA do not account for the failure of T3- thymocytes to proliferate, and changes in surface potential are probably not a necessary early event in activation of T cells by PHA.