Department of Neurology, University of Wuerzburg, Wuerzburg, Germany.
Brain Pathol. 2010 Nov;20(6):999-1009. doi: 10.1111/j.1750-3639.2010.00407.x.
TWIK-related acid-sensitive potassium channels (TASK1-3) belong to the family of two-pore domain (K(2P) ) potassium channels. Emerging knowledge about an involvement of TASK channels in cancer development, inflammation, ischemia and epilepsy puts the spotlight on a leading role of TASK channels under these conditions. TASK3 has been especially linked to cancer development. The pro-oncogenic potential of TASK3 could be shown in cell lines and in various tumor entities. Pathophysiological hallmarks in solid tumors (e.g. low pH and oxygen deprivation) regulate TASK3 channels. These conditions can also be found in (autoimmune) inflammation. Inhibition of TASK1,2,3 leads to a reduction of T cell effector function. It could be demonstrated that TASK1(-/-) mice are protected from experimental autoimmune inflammation while the same animals display increased infarct volumes after cerebral ischemia. Furthermore, TASK channels have both an anti-epileptic as well as a pro-epileptic potential. The relative contribution of these opposing influences depends on their cell type-specific expression and the conditions of the cellular environment. This indicates that TASK channels are per se neither protective nor detrimental but their functional impact depends on the "pathophysiological" scenario. Based on these findings TASK channels have evolved from "mere background" channels to key modulators in pathophysiological conditions.
TWIK 相关酸敏感钾通道（TASK1-3）属于双孔域（K₂P）钾通道家族。关于 TASK 通道参与癌症发展、炎症、缺血和癫痫的新知识，使人们对这些情况下 TASK 通道的主要作用倍加关注。TASK3 尤其与癌症发展有关。TASK3 的致癌潜力在细胞系和各种肿瘤实体中得到了证明。实体肿瘤的病理生理特征（如低 pH 值和缺氧）调节 TASK3 通道。这些条件也存在于（自身免疫）炎症中。抑制 TASK1、2、3 会导致 T 细胞效应功能降低。已经证明，TASK1（-/-）小鼠在实验性自身免疫性炎症中受到保护，而同一动物在脑缺血后梗死体积增加。此外，TASK 通道具有抗癫痫和致癫痫的双重潜能。这些相反影响的相对贡献取决于其细胞类型特异性表达和细胞环境的条件。这表明 TASK 通道本身既没有保护作用也没有损害作用，但其功能影响取决于“病理生理”情况。基于这些发现，TASK 通道已从“单纯背景”通道演变为病理生理条件下的关键调节剂。
