Hvcn1, also known as the voltage-gated hydrogen channel 1, is a member of the voltage-gated ion channel family. Its essential function is to control acid extrusion and regulate pH homeostasis in various cell types. It is involved in multiple biological processes such as intracellular pH regulation, which is crucial for cardiac function, sperm function, and immune cell effector functions [1,2,3,4,5,6]. Genetic models, like knockout mice, are valuable for studying Hvcn1's functions.

In KO mouse models, Hvcn1-deficient mice show splenomegaly, autoantibodies, and nephritis, reminiscent of human autoimmune diseases. The number of activated T-cells is larger in these mice, and upon viral infection, this is remarkably enhanced. Also, the production of superoxide anion in T-cells upon stimulation is significantly attenuated [7]. RNA-seq analysis of murine hearts shows that HVCN1 null hearts exhibit a differential transcriptome profile, with downregulated NADPH oxidoreductases and decreased expression of Cl⁻/HCO₃⁻ exchanger, indicating its role in regulating gene transcriptional networks controlling NOX signaling and CO₂ homeostasis in the heart [5].

In conclusion, Hvcn1 plays a vital role in maintaining pH homeostasis, which is essential for multiple biological processes. The study of Hvcn1 using KO mouse models has revealed its significance in autoimmune-related diseases and cardiac function. Understanding Hvcn1's functions provides insights into the underlying mechanisms of these diseases, potentially guiding the development of new therapeutic strategies.

References:

1. Ma, Jianyong, Gao, Xiaoqian, Li, Yutian, Shull, Gary E, Wang, Hong-Sheng. 2022. The HVCN1 voltage-gated proton channel contributes to pH regulation in canine ventricular myocytes. In The Journal of physiology, 600, 2089-2103. doi:10.1113/JP282126. https://pubmed.ncbi.nlm.nih.gov/35244217/

2. Delgado-Bermúdez, Ariadna, Mateo-Otero, Yentel, Llavanera, Marc, Yeste, Marc, Pinart, Elisabeth. 2021. HVCN1 but Not Potassium Channels Are Related to Mammalian Sperm Cryotolerance. In International journal of molecular sciences, 22, . doi:10.3390/ijms22041646. https://pubmed.ncbi.nlm.nih.gov/33562049/

3. Yeste, Marc, Llavanera, Marc, Mateo-Otero, Yentel, Bonet, Sergi, Pinart, Elisabeth. 2020. HVCN1 Channels Are Relevant for the Maintenance of Sperm Motility During In Vitro Capacitation of Pig Spermatozoa. In International journal of molecular sciences, 21, . doi:10.3390/ijms21093255. https://pubmed.ncbi.nlm.nih.gov/32375375/

4. 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/

5. 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/

6. Zhu, Xiang, Mose, Eucabeth, Zimmermann, Nives. 2013. Proton channel HVCN1 is required for effector functions of mouse eosinophils. In BMC immunology, 14, 24. doi:10.1186/1471-2172-14-24. https://pubmed.ncbi.nlm.nih.gov/23705768/

7. 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/