Laboratory of Medicinal Chemistry and CIRM, University of Liège, 1 Avenue de l'Hôpital, 4000 Liège, Belgium.
Chembiochem. 2011 Aug 16;12(12):1808-12. doi: 10.1002/cbic.201100236. Epub 2011 Jul 1.
Ion-channel function can be modified in various ways. For example, numerous studies have shown that currents through voltage-gated ion channels are affected by pore block or modification of voltage dependence of activation/inactivation. Recent experiments performed on various ion channels show that allosteric modulation is an important mechanism for affecting channel function. For instance, in K(Ca)2 (formerly SK) channels, the prototypic "blocker" apamin prevents conduction by an allosteric mechanism, while TRPV1 channels are prevented from closing by a tarantula toxin, DkTx, through an interaction with residues located away from the selectivity filter. The recent evidence, therefore, suggests that in several ion channels, the region around the outer mouth of the pore is rich in binding sites and could be exploited therapeutically. These discoveries also suggest that the pharmacological vocabulary should be adapted to define these various actions.
离子通道的功能可以通过多种方式进行修饰。例如，大量研究表明，通过电压门控离子通道的电流会受到孔隙阻塞或激活/失活的电压依赖性的改变的影响。最近在各种离子通道上进行的实验表明，变构调节是影响通道功能的重要机制。例如，在 K(Ca)2（以前称为 SK）通道中，典型的“阻断剂”蜂毒素通过变构机制阻止传导，而通过与位于选择性过滤器以外的残基相互作用，蜘蛛毒素 DkTx 可阻止 TRPV1 通道关闭。因此，最近的证据表明，在几种离子通道中，孔隙外口周围的区域富含结合位点，并可用于治疗。这些发现还表明，应该调整药理学词汇来定义这些各种作用。
