Department of Physics, Université de Montréal, Montréal, QC H3T 1J4, Canada.
Department of Pharmacology and Physiology, Université de Montréal, Montréal, QC H3T 1J4, Canada.
Int J Mol Sci. 2024 Aug 17;25(16):8960. doi: 10.3390/ijms25168960.
Migraines are a common type of headache affecting around 15% of the population. The signalling pathways leading to migraines have not been fully understood, but neuronal voltage-gated ion channels, such as KCNG4, have been linked to this pathology. KCNG4 (Kv6.4) is a silent member of the superfamily of voltage-gated potassium (Kv) channels, which expresses in heterotetramers with members of the KCNB (Kv2) family. The genetic variant Kv6.4-L360P has previously been linked to migraines, but their mode of action remains unknown. Here, we characterized the molecular characteristics of Kv6.4-L360P when co-expressed with Kv2.1. We found that Kv6.4-L360P almost completely abolishes Kv2 currents, and we propose that this mechanism in the trigeminal system, linked to the initiation of migraine, leads to the pathology.
偏头痛是一种常见的头痛类型，影响约 15%的人口。导致偏头痛的信号通路尚未完全理解，但神经元电压门控离子通道，如 KCNG4，与这种病理学有关。KCNG4（Kv6.4）是电压门控钾（Kv）通道超家族的沉默成员，与 KCNB（Kv2）家族的成员表达为异四聚体。先前已将 Kv6.4-L360P 遗传变异与偏头痛联系起来，但它们的作用机制仍不清楚。在这里，我们描述了 Kv6.4-L360P 与 Kv2.1 共表达时的分子特征。我们发现 Kv6.4-L360P 几乎完全消除 Kv2 电流，我们提出这种与偏头痛发作有关的三叉神经系统中的机制导致了这种病理学。
