Hvcn1, also known as the voltage-gated hydrogen channel 1, is a member of the voltage-gated ion channel family. Its primary function is to control acid extrusion and regulate pH homeostasis in various cell types. It is involved in multiple biological processes such as phagocytosis, B-cell activation, sperm physiology, and cardiac function. Genetic models, like gene knockout mice, are valuable for studying Hvcn1's functions [1,2].

In cardiac myocytes, RNA-seq analysis of murine hearts showed that Hvcn1 null hearts had an impaired pH homeostasis with downregulated NADPH oxidoreductases (NOXs) and decreased expression of Cl⁻/HCO₃⁻ exchanger, indicating its role in regulating gene transcriptional networks controlling NOX signaling and CO₂ homeostasis. These hearts also had differential expression of cardiac ion channels, suggesting a potential role in cardiac electrophysiological remodeling [2]. In microglia/macrophages, both genetic deletion of the Hvcn1 gene in vitro and neutralization of Hvcn1 with antibody in vivo promoted their migration and myelin debris clearance, uncovering a new role of Hvcn1 in these cells [3]. Hvcn1-deficient mice showed splenomegaly, autoantibodies, and nephritis, similar to human autoimmune disease phenotypes, with an increased number of activated T-cells and attenuated superoxide anion production in T-cells upon stimulation, suggesting Hvcn1 regulates T-cell homeostasis in vivo [4].

In conclusion, Hvcn1 is crucial for pH regulation and various cellular functions. Studies using gene knockout mouse models have revealed its significance in cardiac function, microglia/macrophage migration, and T-cell homeostasis, providing insights into its role in diseases related to these processes, such as heart diseases and autoimmune disorders.

References:

1. Capasso, Melania, DeCoursey, Thomas E, Dyer, Martin J S. 2010. pH regulation and beyond: unanticipated functions for the voltage-gated proton channel, HVCN1. In Trends in cell biology, 21, 20-8. doi:10.1016/j.tcb.2010.09.006. https://pubmed.ncbi.nlm.nih.gov/20961760/

2. Wu, Xin, Li, Yawei, Maienschein-Cline, Mark, Wu, Longjun, Hong, Liang. 2022. RNA-Seq Analyses Reveal Roles of the HVCN1 Proton Channel in Cardiac pH Homeostasis. In Frontiers in cell and developmental biology, 10, 860502. doi:10.3389/fcell.2022.860502. https://pubmed.ncbi.nlm.nih.gov/35372367/

3. Wang, Fan, Ma, Xiao-Ru, Wu, Yang, Wang, Li-Bin, Zhao, Jing-Wei. 2021. Neutralization of Hv1/HVCN1 With Antibody Enhances Microglia/Macrophages Myelin Clearance by Promoting Their Migration in the Brain. In Frontiers in cellular neuroscience, 15, 768059. doi:10.3389/fncel.2021.768059. https://pubmed.ncbi.nlm.nih.gov/34744634/

4. Sasaki, Mari, Tojo, Akihiro, Okochi, Yoshifumi, Murakami, Masaaki, Okamura, Yasushi. . Autoimmune disorder phenotypes in Hvcn1-deficient mice. In The Biochemical journal, 450, 295-301. doi:10.1042/BJ20121188. https://pubmed.ncbi.nlm.nih.gov/23231444/