Kcnj5, encoding GIRK4 (a subunit of the G-protein-gated inwardly rectifying potassium (GIRK) channels), is crucial for the functional KACh channel within the heart, modulating the parasympathetic nervous system's influence on cardiac physiology [1]. It is also associated with the pathogenesis of primary aldosteronism (PA), especially in aldosterone-producing adenoma (APA), where its somatic mutations are common, particularly in Asian countries [2].

In primary aldosteronism, Kcnj5 somatic mutations in APA patients are related to younger age, female gender, higher aldosterone levels, lower potassium levels, larger tumor size, and a higher hypertension cure rate after adrenalectomy [2]. These mutations also lead to distinct cardiovascular and metabolic impacts, such as higher left ventricular mass, more impaired diastolic function, thicker aortic wall, and a lower incidence of metabolic syndrome, with better post-adrenalectomy improvement in some parameters compared to non-mutated patients [2]. In addition, Kcnj5 mutations in APA are more frequent in women in Western populations [3]. Regarding adrenal cell growth in APA with Kcnj5 mutations, the Ki67 proliferative index shows a positive correlation with adenoma diameter, and different mutations have various effects on cell proliferation and apoptosis [4].

In conclusion, Kcnj5 is essential for cardiac physiology and is deeply involved in the pathogenesis of primary aldosteronism, especially in APA. Research on Kcnj5, including through in-vivo studies and potentially gene knockout models, helps to understand its role in these biological processes and disease conditions, which may provide insights for treating related cardiovascular and endocrine diseases.

References:

1. Meyer, Karisa M, Malhotra, Nipun, Kwak, Jung Seo, El Refaey, Mona. 2023. Relevance of KCNJ5 in Pathologies of Heart Disease. In International journal of molecular sciences, 24, . doi:10.3390/ijms241310849. https://pubmed.ncbi.nlm.nih.gov/37446026/

2. Chang, Yi-Yao, Lee, Bo-Ching, Chen, Zheng-Wei, Hung, Chi-Sheng, Lin, Yen-Hung. 2023. Cardiovascular and metabolic characters of KCNJ5 somatic mutations in primary aldosteronism. In Frontiers in endocrinology, 14, 1061704. doi:10.3389/fendo.2023.1061704. https://pubmed.ncbi.nlm.nih.gov/36950676/

3. Williams, T A, Lenders, J W M, Burrello, J, Beuschlein, F, Reincke, M. 2015. KCNJ5 Mutations: Sex, Salt and Selection. In Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 47, 953-8. doi:10.1055/s-0035-1565090. https://pubmed.ncbi.nlm.nih.gov/26566104/

4. Yang, Yuhong, Gomez-Sanchez, Celso E, Jaquin, Diana, Reincke, Martin, Williams, Tracy Ann. 2019. Primary Aldosteronism: KCNJ5 Mutations and Adrenocortical Cell Growth. In Hypertension (Dallas, Tex. : 1979), 74, 809-816. doi:10.1161/HYPERTENSIONAHA.119.13476. https://pubmed.ncbi.nlm.nih.gov/31446799/