Kcne3, also known as MiRP2, is a single transmembrane-spanning ion channel regulatory subunit belonging to the human KCNE gene family. Its primary function is to regulate voltage-gated potassium (Kv) channels, especially in complex with the KCNQ1 Kv α subunit. In the intestine, constitutively active KCNQ1-KCNE3 channels are important for potassium and chloride secretion. It also plays a role in other physiological processes and is associated with various diseases, highlighting its biological importance. Genetic models, such as gene-knockout mouse models, are valuable for studying its function [1,2,5,6].

In Kcne3 -/- mice, the deletion led to several significant findings. There was an activated-lymphocyte adrenal infiltration, secondary hyperaldosteronism, and a subsequent impairment of ventricular repolarization, predisposing the mice to post-ischemia arrhythmogenesis. This shows that Kcne3 deletion is arrhythmogenic through a novel mechanism involving extracardiac pathogenesis [3]. Additionally, Kcne3 deletion in mice was found to increase oxidative metabolic gene expression in gastrocnemius muscle, remodel K⁺ channel α-subunits, and impair skeletal muscle function, as evidenced by abnormal hind-limb clasping and changes in muscle contractile force [4].

In conclusion, Kcne3 is crucial for regulating potassium channels in various tissues. Model-based research, particularly the use of Kcne3 KO mouse models, has revealed its role in cardiac arrhythmias and skeletal muscle function. Understanding Kcne3's functions provides insights into the pathogenesis of related diseases and may offer potential therapeutic targets [3,4].

References:

1. Abbott, Geoffrey W. 2015. KCNE1 and KCNE3: The yin and yang of voltage-gated K(+) channel regulation. In Gene, 576, 1-13. doi:10.1016/j.gene.2015.09.059. https://pubmed.ncbi.nlm.nih.gov/26410412/

2. Barro-Soria, Rene, Perez, Marta E, Larsson, H Peter. 2015. KCNE3 acts by promoting voltage sensor activation in KCNQ1. In Proceedings of the National Academy of Sciences of the United States of America, 112, E7286-92. doi:10.1073/pnas.1516238112. https://pubmed.ncbi.nlm.nih.gov/26668384/

3. Hu, Zhaoyang, Crump, Shawn M, Anand, Marie, Levi, Roberto, Abbott, Geoffrey W. 2013. Kcne3 deletion initiates extracardiac arrhythmogenesis in mice. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 28, 935-45. doi:10.1096/fj.13-241828. https://pubmed.ncbi.nlm.nih.gov/24225147/

4. King, Elizabeth C, Patel, Vishal, Anand, Marie, Weisleder, Noah, Abbott, Geoffrey W. 2017. Targeted deletion of Kcne3 impairs skeletal muscle function in mice. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 31, 2937-2947. doi:10.1096/fj.201600965RR. https://pubmed.ncbi.nlm.nih.gov/28356343/

5. Asare, Isaac K, Galende, Alberto Perez, Garcia, Andres Bastidas, Lorigan, Gary A, Sahu, Indra D. 2022. Investigating Structural Dynamics of KCNE3 in Different Membrane Environments Using Molecular Dynamics Simulations. In Membranes, 12, . doi:10.3390/membranes12050469. https://pubmed.ncbi.nlm.nih.gov/35629795/

6. Kroncke, Brett M, Van Horn, Wade D, Smith, Jarrod, Vanoye, Carlos G, Sanders, Charles R. 2016. Structural basis for KCNE3 modulation of potassium recycling in epithelia. In Science advances, 2, e1501228. doi:10.1126/sciadv.1501228. https://pubmed.ncbi.nlm.nih.gov/27626070/