Greenwood Iain A, Leblanc Normand
Ion Channels and Cell Signalling Research Centre, Division of Basic Medical Sciences, St George's, University of London, London SW17 0RE, UK.
Trends Pharmacol Sci. 2007 Jan;28(1):1-5. doi: 10.1016/j.tips.2006.11.004. Epub 2006 Dec 5.
Research into Ca2+-activated Cl- channels is hampered by the inability to decipher their molecular identity and the fact that all extant Cl- channel blockers have effects on other ion channels. Most notably, Cl- channel blockers such as the fenamates (e.g. niflumic acid and flufenamic acid) activate Ca2+-dependent K+ channels, although other pharmacological overlaps have been discovered. In this article, we highlight the complex pharmacology of Ca2+-activated Cl- channels and the caveats associated with using these blockers--a necessary requirement because many researchers use Cl- channel blockers as probes for Cl- channel activity. Moreover, we discuss the argument for a common structural motif between Ca2+-activated Cl- channels and Ca2+-dependent K+ channels, which has led to the possibility that the molecular identity of Cl- channels will be revealed by research in this new direction, in addition to the use of existing candidates such as the CLCA, Bestrophin and tweety genes.
由于无法确定其分子身份，以及所有现存的氯离子通道阻滞剂都会对其他离子通道产生影响，钙离子激活氯离子通道的研究受到了阻碍。最值得注意的是，诸如非甾体抗炎药（如氟尼辛和氟芬那酸）之类的氯离子通道阻滞剂会激活钙离子依赖性钾通道，不过也发现了其他药理学上的重叠现象。在本文中，我们强调了钙离子激活氯离子通道复杂的药理学特性以及使用这些阻滞剂时的注意事项——这是必要的要求，因为许多研究人员将氯离子通道阻滞剂用作氯离子通道活性的探针。此外，我们还讨论了钙离子激活氯离子通道与钙离子依赖性钾通道之间存在共同结构基序的观点，这除了利用现有的候选基因（如CLCA、Bestrophin和tweety基因）之外，还使得通过这个新方向的研究揭示氯离子通道分子身份成为可能。
