Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Neurosci Lett. 2022 Jan 19;769:136376. doi: 10.1016/j.neulet.2021.136376. Epub 2021 Nov 28.
TWIK-related spinal cord potassium (TRESK) and TWIK-related potassium (TREK) channels are both subfamilies of the two-pore domain potassium (K2P) channel group. Despite major structural, pharmacological, as well as biophysical differences, emerging data suggest that channels of these two subfamilies are functionally more closely related than previously assumed. Recent studies, for instance, indicate an assembling of TRESK and TREK subunits, leading to the formation of heterodimeric channels with different functional properties compared to homodimeric ones. Formation of tandems consisting of TRESK and TREK subunits might thus multiply the functional diversity of both TRESK and TREK activity. Based on the involvement of these channels in the pathophysiology of migraine, we here highlight the role as well as the impact of the interplay of TRESK and TREK subunits in the context of different disease settings. In this regard, we focus on their involvement in migraine and pain syndromes, as well as on their influence on (neuro-)inflammatory processes. Furthermore, we describe the potential implications for innovative therapeutic strategies that take advantage of TRESK and TREK modulation as well as obstacles encountered in the development of therapies related to the aforementioned diseases.
TWIK 相关的脊髓钾 (TRESK) 和 TWIK 相关的钾 (TREK) 通道均为双孔域钾 (K2P) 通道家族的亚家族。尽管存在主要的结构、药理学和生物物理差异，但新出现的数据表明，这两个亚家族的通道在功能上比以前假设的更为密切相关。例如，最近的研究表明 TRESK 和 TREK 亚基的组装，导致形成具有与同二聚体不同的功能特性的异二聚体通道。由 TRESK 和 TREK 亚基组成的串联的形成因此可能使 TRESK 和 TREK 活性的功能多样性倍增。基于这些通道参与偏头痛的病理生理学，我们在此强调了 TRESK 和 TREK 亚基相互作用在不同疾病环境中的作用及其影响。在这方面，我们专注于它们在偏头痛和疼痛综合征中的参与，以及它们对（神经）炎症过程的影响。此外，我们描述了利用 TRESK 和 TREK 调节以及与上述疾病相关的治疗开发中遇到的障碍的创新治疗策略的潜在意义。
