Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, USA.
Purdue University Center for Cancer Research, West Lafayette, Indiana, USA.
Dev Dyn. 2021 Oct;250(10):1477-1493. doi: 10.1002/dvdy.329. Epub 2021 Mar 24.
Calcium-activated potassium channels (KCa) are a specific type of potassium channel activated by intracellular calcium concentration changes. This group of potassium channels plays fundamental roles ranging from regulating neuronal excitability to immune cell activation. Many human diseases such as schizophrenia, hypertension, epilepsy, and cancers have been linked to mutations in this group of potassium channels. Although the KCa channels have been extensively studied electrophysiologically and pharmacologically, their spatiotemporal gene expression during embryogenesis remains mostly unknown.
Using zebrafish as a model, we identified and renamed 14 KCa genes. We further performed phylogenetic and syntenic analyses on vertebrate KCa genes. Our data revealed that the number of KCa genes in zebrafish was increased, most likely due to teleost-specific whole-genome duplication. Moreover, we examined zebrafish KCa gene expression during early embryogenesis. The duplicated ohnologous genes show distinct and overlapped gene expression. Furthermore, we found that zebrafish KCa genes are expressed in various tissues and organs (somites, fins, olfactory regions, eye, kidney, and so on) and neuronal tissues, suggesting that they may play important roles during zebrafish embryogenesis.
Our phylogenetic and developmental analyses shed light on the potential functions of the KCa genes during embryogenesis related to congenital diseases and human channelopathies.
钙激活钾通道(KCa)是一种特定类型的钾通道,由细胞内钙离子浓度变化激活。这组钾通道在从调节神经元兴奋性到免疫细胞激活的基本功能中发挥作用。许多人类疾病,如精神分裂症、高血压、癫痫和癌症,都与这组钾通道的突变有关。尽管 KCa 通道在电生理学和药理学上已经得到了广泛的研究,但它们在胚胎发生过程中的时空基因表达仍然知之甚少。
我们使用斑马鱼作为模型,鉴定并重新命名了 14 个 KCa 基因。我们进一步对脊椎动物 KCa 基因进行了系统发生和基因同线性分析。我们的数据表明,斑马鱼 KCa 基因的数量增加了,这很可能是由于硬骨鱼特异性的全基因组复制所致。此外,我们检测了斑马鱼早期胚胎发育过程中的 KCa 基因表达。重复的同源基因表现出不同但重叠的基因表达。此外,我们发现斑马鱼 KCa 基因在各种组织和器官(体节、鳍、嗅觉区、眼睛、肾脏等)和神经元组织中表达,表明它们可能在斑马鱼胚胎发生过程中发挥重要作用。
我们的系统发生和发育分析为 KCa 基因在胚胎发生过程中与先天性疾病和人类通道病相关的潜在功能提供了线索。