Kunzelmann Karl
Institut für Physiologie, Universität Regensburg, Universitätsstrasse 31, Regensburg, D-93053, Germany.
J Membr Biol. 2005 Jun;205(3):159-73. doi: 10.1007/s00232-005-0781-4.
Membrane ion channels are essential for cell proliferation and appear to have a role in the development of cancer. This has initially been demonstrated for potassium channels and is meanwhile also suggested for other cation channels and Cl- channels. For some of these channels, like voltage-gated ether à go-go and Ca2+-dependent potassium channels as well as calcium and chloride channels, a cell cycle-dependent function has been demonstrated. Along with other membrane conductances, these channels control the membrane voltage and Ca2+ signaling in proliferating cells. Homeostatic parameters, such as the intracellular ion concentration, cytosolic pH and cell volume, are also governed by the activity of ion channels. Thus it will be an essential task for future studies to unravel cell cycle-specific effects of ion channels and non-specific homeostatic functions. When studying the role of ion channels in cancer cells, it is indispensable to choose experimental conditions that come close to the in vivo situation. Thus, environmental parameters, such as low oxygen pressure, acidosis and exposure to serum proteins, have to be taken into account. In order to achieve clinical application, more studies on the original cancer tissue are required, and improved animal models. Finally, it will be essential to generate more potent and specific inhibitors of ion channels to overcome the shortcomings of some of the current approaches.
膜离子通道对于细胞增殖至关重要,并且似乎在癌症发展中发挥作用。这最初是针对钾通道得到证实的,同时也有人提出其他阳离子通道和氯离子通道也有此作用。对于其中一些通道,如电压门控的超极化激活环核苷酸门控钾通道、钙依赖性钾通道以及钙通道和氯通道,其细胞周期依赖性功能已得到证实。与其他膜电导一起,这些通道控制着增殖细胞中的膜电压和钙信号。细胞内离子浓度、胞质pH值和细胞体积等稳态参数也受离子通道活性的调控。因此,揭示离子通道的细胞周期特异性效应和非特异性稳态功能将是未来研究的一项重要任务。在研究离子通道在癌细胞中的作用时,选择接近体内情况的实验条件是必不可少的。因此,必须考虑环境参数,如低氧压力、酸中毒和暴露于血清蛋白。为了实现临床应用,需要对原发性癌组织进行更多研究,并改进动物模型。最后,开发更有效、更特异的离子通道抑制剂以克服当前一些方法的缺点将至关重要。