ArticleCardiovascular research2019
Downregulation of BK channel function and protein expression in coronary arteriolar smooth muscle cells of type 2 diabetic patients.
Article in Cardiovascular research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Impact of Sorbs2 dysfunction on cardiovascular diseases.Biochimica et biophysica acta. Molecular basis of disease · 2025Review
- Single-cell transcriptomic analysis of the human vascular atlas provides new insights into vasorelaxation redundancy and heterogeneity.Frontiers in cardiovascular medicine · 2025Article
- Emerging connections between Piezo1 and BK channels in vascular smooth muscle cells.Pflugers Archiv : European journal of physiology · 2024Article
- Oxidative and Nitrous Stress Underlies Vascular Malfunction Induced by Ionizing Radiation and Diabetes.Cardiovascular toxicology · 2024Review
- Aerobic exercise improves BKActa diabetologica · 2024Article
- Sorbs2 Deficiency and Vascular BK Channelopathy in Diabetes.Circulation research · 2024Article
- Cycling matters: Sex hormone regulation of vascular potassium channels.Channels (Austin, Tex.) · 2023Review
- Activating BK channels ameliorates vascular smooth muscle calcification through Akt signaling.Acta pharmacologica Sinica · 2022Article
- Large-conductance CaFrontiers in cardiovascular medicine · 2022Article
- Neonatal Diabetes in Patients Affected by Liang-Wang Syndrome Carrying KCNMA1 Variant p.(Gly375Arg) Suggest a Potential Role of CaCurrent issues in molecular biology · 2021Article
- Coronary Large Conductance CaFrontiers in physiology · 2021Review
- Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle.Cellular and molecular life sciences : CMLS · 2021Review
- Regulation of KCNMA1 transcription by Nrf2 in coronary arterial smooth muscle cells.Journal of molecular and cellular cardiology · 2020Article
- BK Channel Dysfunction in Diabetic Coronary Artery: Role of the E3 Ubiquitin Ligases.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
Aims: Type 2 diabetes (T2D) is strongly associated with cardiovascular morbidity and mortality in patients. Vascular large conductance Ca2+-activated potassium (BK) channels, composed of four pore-forming α subunits (BK-α), and four regulatory β1 subunits (BK-β1), are densely expressed in coronary arterial smooth muscle cells (SMCs) and play an important role in regulating vascular tone and myocardial perfusion. However, the role of BK channels in coronary microvascular dysfunction of human subjects with diabetes is unclear. In this study, we examined BK channel function and protein expression, and BK channel-mediated vasodilation in freshly isolated coronary arterioles from T2D patients. Methods and results: Atrial tissues were obtained from 16 patients with T2D and 25 matched non-diabetic subjects during cardiopulmonary bypass procedure. Microvessel videomicroscopy and immunoblot analysis were performed in freshly dissected coronary arterioles and inside-out single BK channel currents was recorded in enzymatically isolated coronary arteriolar SMCs. We found that BK channel sensitivity to physiological Ca2+ concentration and voltage was downregulated in the coronary arteriolar SMCs of diabetic patients, compared with non-diabetic controls. BK channel kinetics analysis revealed that there was significant shortening of the mean open time and prolongation of the mean closed time in diabetic patients, resulting in a remarkable reduction of the channel open probability. Functional studies showed that BK channel activation by dehydrosoyasaponin-1 was diminished and that BK channel-mediated vasodilation in response to shear stress was impaired in diabetic coronary arterioles. Immunoblot experiments confirmed that the protein expressions of BK-α and BK-β1 subunits were significantly downregulated, but the ratio of BK-α/BK-β1 was unchanged in the coronary arterioles of T2D patients. Conclusions: Our results demonstrated for the first time that BK channel function and BK channel-mediated vasodilation were abnormal in the coronary microvasculature of diabetic patients, due to decreased protein expression and altered intrinsic properties of BK channels.
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