Table1_RNA-Seq Analyses Reveal Roles of the HVCN1 Proton Channel in Cardiac pH Homeostasis.XLSX

The voltage-gated proton channel HVCN1 is a member of the voltage-gated ion channel family. HVCN1 channel controls acid extrusion and regulates pH homeostasis in various cell types. Recent evidence indicated that the HVCN1 channel was associated with cardiac function. To investigate the role of HVCN1 in cardiac myocytes, we performed an RNA sequencing analysis of murine hearts and showed that HVCN1 null hearts exhibited a differential transcriptome profile compared with wild-type hearts. The RNA-seq data indicating impaired pH homeostasis in HVCN1 null hearts were the downregulated NADPH oxidoreductases (NOXs) and decreased expression of Cl−/HCO3− exchanger, indicating HVCN1 is a regulator of gene transcriptional networks controlling NOX signaling and CO2 homeostasis in the heart. Additionally, HVCN1 null hearts exhibited differential expression of cardiac ion channels, suggesting a potential role of HVCN1 in cardiac electrophysiological remodeling. The study highlights the importance of HVCN1 in cardiac function and may present a novel target associated with heart diseases.

电压门控质子通道HVCN1（voltage-gated proton channel）隶属于电压门控离子通道家族。该通道可介导酸排出过程，并在多种细胞类型中调控pH稳态。近期研究表明，HVCN1通道与心脏功能密切相关。为探究HVCN1在心肌细胞中的作用，本研究对小鼠心脏开展了RNA测序分析，结果显示，与野生型小鼠心脏相比，HVCN1基因缺失小鼠心脏的转录组表达谱存在显著差异。RNA测序数据显示，HVCN1基因缺失小鼠心脏存在pH稳态受损的情况，具体表现为NADPH氧化酶（NADPH oxidoreductases，NOXs）表达下调以及Cl⁻/HCO₃⁻交换体表达水平降低，这表明HVCN1是调控心脏中NOX信号通路与CO₂稳态的基因转录网络的调节因子。此外，HVCN1基因缺失小鼠心脏的心肌离子通道表达谱存在显著差异，提示HVCN1可能参与心脏电生理重构。本研究凸显了HVCN1在心脏功能中的重要性，或可成为心脏疾病相关的新型治疗靶点。