Department of Physiology, Semmelweis University, Budapest, Hungary.
Mol Cell Endocrinol. 2012 Apr 28;353(1-2):75-81. doi: 10.1016/j.mce.2011.11.009. Epub 2011 Nov 17.
TRESK (TWIK-related spinal cord K(+) channel, KCNK18) belongs to the two-pore domain (K2P) background (leak) potassium channel family. Unlike other K2P channels, TRESK is activated by the calcium signal in heterologous expression systems. The activation is mediated by the calcium/calmodulin-dependent protein phosphatase, calcineurin. TRESK is abundantly expressed in dorsal root and trigeminal ganglia. The active ingredient of Sichuan pepper, sanshool, has been suggested to evoke tingling paresthesia by inhibiting the channel in a mechanoreceptor subpopulation of sensory neurons. Recently, dominant-negative mutation of human TRESK was found to be linked to migraine with aura in a large pedigree. It is hoped that future TRESK agonists may prevent or ameliorate the debilitating symptoms of migraine. It will be interesting to see whether the calcineurin-activated K(+) channel maintains normal excitability in the cerebral cortex thereby arresting cortical spreading depression (CSD), or prevents migraine attack only in the trigeminovascular (TGVS) system.
TRESK（TWIK 相关的脊髓 K(+)通道，KCNK18）属于双孔域（K2P）背景（泄漏）钾通道家族。与其他 K2P 通道不同，TRESK 在异源表达系统中被钙信号激活。这种激活是由钙/钙调蛋白依赖性蛋白磷酸酶，钙调神经磷酸酶介导的。TRESK 在背根神经节和三叉神经节中大量表达。四川花椒的活性成分，花椒麻素，被认为通过抑制感觉神经元机械感受器亚群中的通道引起刺痛感觉异常。最近，在一个大型家系中发现人类 TRESK 的显性负突变与有先兆偏头痛有关。人们希望未来的 TRESK 激动剂可以预防或改善偏头痛的致残症状。有趣的是，钙调神经磷酸酶激活的 K(+)通道是否会保持大脑皮层的正常兴奋性从而阻止皮质扩散性抑制（CSD），或者仅在三叉血管系统（TGVS）中预防偏头痛发作。
