Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan 1;31(1):129-134.
doi: 10.1097/MNH.0000000000000751.

KCa3.1 in diabetic kidney disease

Chunling Huang  1 , Xin-Ming Chen, Carol A Pollock
Affiliations
Review

KCa3.1 in diabetic kidney disease

Chunling Huang et al. Curr Opin Nephrol Hypertens. .

Abstract

Purpose of review: Diabetic kidney disease (DKD) is a significant health concern. Innovative strategies to prevent or limit the progression of DKD are urgently needed due to the limitation of existing treatments. KCa3.1, a potassium channel, is involved in a range of biological processes from cell survival to cell death. This review summarizes the current knowledge on the pathophysiological functions of the KCa3.1 channel, specifically its involvement in maintaining mitochondrial function. More specifically, the therapeutic potential of targeting KCa3.1 in DKD is systematically discussed in the review.

Recent findings: Mitochondrial dysfunction contributes to the development and progression of DKD. Accumulating evidence indicates that KCa3.1 dysregulation plays a crucial role in mitochondrial dysfunction, in addition to driving cellular activation, proliferation and inflammation. Recent studies demonstrate that KCa3.1 deficiency improves diabetes-induced mitochondrial dysfunction in DKD, which is attributed to modulation of mitochondrial quality control through mitigating the altered mitochondrial dynamics and restoring abnormal BNIP3-mediated mitophagy.

Summary: Based on its role in fibrosis, inflammation and mitochondrial dysfunction, pharmacological inhibition of KCa3.1 may offer a promising alternative for the treatment of DKD. Due to its safety profile in humans, the repurposing of senicapoc has the potential to expedite an urgently needed new drug in DKD.

PubMed Disclaimer

References

    1. Sugahara M, Pak WLW, Tanaka T, et al. Update on diagnosis, pathophysiology, and management of diabetic kidney disease. Nephrology (Carlton) 2021; 26:491–500.
    1. Leoncini G, Viazzi F, De Cosmo S, et al. Blood pressure reduction and RAAS inhibition in diabetic kidney disease: therapeutic potentials and limitations. J Nephrol 2020; 33:949–963.
    1. DeFronzo RA, Reeves WB, Awad AS. Pathophysiology of diabetic kidney disease: impact of SGLT2 inhibitors. Nat Rev Nephrol 2021; 17:319–334.
    1. Giacomello M, Pyakurel A, Glytsou C, Scorrano L. The cell biology of mitochondrial membrane dynamics. Nat Rev Mol Cell Biol 2020; 21:204–224.
    1. Xu J, Kitada M, Koya D. The impact of mitochondrial quality control by Sirtuins on the treatment of type 2 diabetes and diabetic kidney disease. Biochim Biophys Acta Mol Basis Dis 2020; 1866:165756.

LinkOut - more resources