Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle

• Published in: Cellular and molecular life sciences : CMLS 2021-01, Vol.78 (1), p.31-61
• Main Authors: Nieves-Cintrón, Madeline, Flores-Tamez, Víctor A., Le, Thanhmai, Baudel, Miguel Martín-Aragón, Navedo, Manuel F.
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Blood vessels; Calcium channels; Calcium channels (L-type); Calcium channels (voltage-gated); Calcium Channels - metabolism; Calcium ions; Cardiovascular diseases; Cell Biology; Cyclic AMP-Dependent Protein Kinases - metabolism; Diabetes; Diabetes mellitus; Diabetes Mellitus - metabolism; Diabetes Mellitus - pathology; Endothelial Cells - metabolism; Glucose - metabolism; Humans; Hyperglycemia; Hyperglycemia - metabolism; Hyperglycemia - pathology; Ion channels; Ion Channels - metabolism; Life Sciences; Muscle function; Muscle, Smooth, Vascular - metabolism; Muscles; Pathogenesis; Potassium channels (voltage-gated); Review; Smooth muscle
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-020-03582-z

Diabetes affects millions of people worldwide. This devastating disease dramatically increases the risk of developing cardiovascular disorders. A hallmark metabolic abnormality in diabetes is hyperglycemia, which contributes to the pathogenesis of cardiovascular complications. These cardiovascular complications are, at least in part, related to hyperglycemia-induced molecular and cellular changes in the cells making up blood vessels. Whereas the mechanisms mediating endothelial dysfunction during hyperglycemia have been extensively examined, much less is known about how hyperglycemia impacts vascular smooth muscle function. Vascular smooth muscle function is exquisitely regulated by many ion channels, including several members of the potassium (K + ) channel superfamily and voltage-gated L-type Ca 2+ channels. Modulation of vascular smooth muscle ion channels function by hyperglycemia is emerging as a key contributor to vascular dysfunction in diabetes. In this review, we summarize the current understanding of how diabetic hyperglycemia modulates the activity of these ion channels in vascular smooth muscle. We examine underlying mechanisms, general properties, and physiological relevance in the context of myogenic tone and vascular reactivity.