KCNA5, encoding the voltage-gated potassium channel Kv1.5, is involved in regulating diverse functions. It participates in the regulation of atrial cardiac action potential, the activity of vascular smooth muscle cells, insulin release, and tumour cell proliferation. The ubiquitin ligase Nedd4-2, a known regulator of Kv1.5, can be modified by SGK3, which in turn affects KCNA5 activity [4].

Reduced expression and/or activity of Kv1.5 channels (encoded by KCNA5) is a common feature in human or experimental pulmonary arterial hypertension (PAH). Some KCNA5 variants (e.g., Arg184Pro and Gly384Arg) found in PAH patients lead to a loss of potassium channel function and affect apoptosis, suggesting that KCNA5 pathogenic variants may contribute to PAH [1]. In atrial fibrillation (AF), the expressions of KCNA5, Cx43, and Cx40 were substantially downregulated, and KCNA5 interacted with Cx43 and Cx40 proteins [2]. Also, in breast cancer, caveolin-1 facilitated KCNA5 expression, which may be associated with AKT activation and breast cancer cell viability [3].

In conclusion, KCNA5 is crucial for multiple physiological and pathological processes. Its role in diseases such as PAH, AF, and breast cancer has been revealed through functional studies. Understanding KCNA5's function provides insights into the mechanisms of these diseases, potentially offering new directions for diagnosis and treatment.

References:

1. Vera-Zambrano, Alba, Lago-Docampo, Mauro, Gallego, Natalia, González, Teresa, Cogolludo, Angel. . Novel Loss-of-Function KCNA5 Variants in Pulmonary Arterial Hypertension. In American journal of respiratory cell and molecular biology, 69, 147-158. doi:10.1165/rcmb.2022-0245OC. https://pubmed.ncbi.nlm.nih.gov/36917789/

2. Wang, Keke, Zhao, Juntao, Guo, Zhikun. 2022. Interaction of KCNA5, CX43, and CX40 proteins in the atrial muscle of patients with atrial fibrillation. In Cell biology international, 46, 1834-1840. doi:10.1002/cbin.11864. https://pubmed.ncbi.nlm.nih.gov/35870168/

3. Qu, Chao, Sun, Jia, Liu, Ying, Zou, Wei, Liu, Jing. 2018. Caveolin-1 facilitated KCNA5 expression, promoting breast cancer viability. In Oncology letters, 16, 4829-4838. doi:10.3892/ol.2018.9261. https://pubmed.ncbi.nlm.nih.gov/30250548/

4. Ahmed, Musaab, Fezai, Myriam, Uzcategui, Nestor L, Hosseinzadeh, Zohreh, Lang, Florian. 2016. SGK3 Sensitivity of Voltage Gated K+ Channel Kv1.5 (KCNA5). In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 38, 359-67. doi:10.1159/000438636. https://pubmed.ncbi.nlm.nih.gov/26824455/