4.7 Article

RNA-Seq Analyses Reveal Roles of the HVCN1 Proton Channel in Cardiac pH Homeostasis

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.860502

Keywords

HVCN1; RNA-seq; NOX; pH homeostasis; heart

Funding

  1. National Institute of Health [R01GM139991]
  2. American Heart Association [19CDA34630041]
  3. NCATS [UL1TR002003]

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The voltage-gated proton channel HVCN1 plays a crucial role in regulating pH homeostasis and controlling cardiac function. RNA sequencing analysis revealed differential transcriptome profiles and cardiac ion channel expression in HVCN1 null hearts, pointing towards a potential impact on cardiac electrophysiological remodeling.
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.

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