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Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
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Sorbs2 Deficiency and Vascular BK Channelopathy in Diabetes
Xiaojing Sun1, Hon-Chi Lee1, Tong Lu1
1The Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
Circulation Research
|February 16, 2024
Summary
Sorbs2 protein regulates vascular BK channel function and expression. Its downregulation in diabetes causes coronary artery dysfunction, mimicking diabetic vasculopathy.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Vascular Physiology
Background:
- The large conductance Ca2+-activated K+ (BK) channel is crucial for coronary vasodilation but is impaired in diabetes.
- The role of Sorbs2 (Sorbin homology and Src homology 3 domains-containing protein 2) in vascular function and diabetes is unknown.
Purpose of the Study:
- To investigate the role of Sorbs2 in regulating vascular BK channel activity and its relevance in diabetic vasculopathy.
Main Methods:
- Patch-clamp recordings, molecular biology techniques, and in silico analysis were used.
- Sorbs2 interaction with BK channel subunits and mRNA was examined.
- Nrf2 regulation of Sorbs2 and Sorbs2 knockout mouse models were studied.
Main Results:
- Sorbs2 binds to BK channel subunits and mRNA, regulating channel expression and function.
- Sorbs2 is an Nrf2 target gene, and its expression is downregulated in diabetic mouse arteries.
- Sorbs2 knockout mice exhibit decreased BK channel function and impaired vasodilation, similar to diabetic conditions.
Conclusions:
- Sorbs2 regulates BK channel expression and function in vascular smooth muscle cells.
- Vascular Sorbs2 is downregulated in diabetes, contributing to coronary BK channelopathy and vasculopathy.
- Sorbs2 deficiency in mice recapitulates diabetic vascular dysfunction independently of obesity and hyperglycemia.
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