Impaired BK_Ca channel function in native vascular smooth muscle from humans with type 2 diabetes

Large-conductance Ca²⁺-activated potassium (BK_Ca) channels are key determinants of vascular smooth muscle excitability. Impaired BK_Ca channel function through remodeling of BK_Ca β1 expression and function contributes to vascular complications in animal models of diabetes. Yet, whether similar alterations occur in native vascular smooth muscle from humans with type 2 diabetes is unclear. In this study, we evaluated BK_Ca function in vascular smooth muscle from small resistance adipose arteries of non-diabetic and clinically diagnosed type 2 diabetic patients. We found that BK_Ca channel activity opposes pressure-induced constriction in human small resistance adipose arteries, and this is compromised in arteries from diabetic patients. Consistent with impairment of BK_Ca channel function, the amplitude and frequency of spontaneous BK_Ca currents, but not Ca²⁺ sparks were lower in cells from diabetic patients. BK_Ca channels in diabetic cells exhibited reduced Ca²⁺ sensitivity, single-channel open probability and tamoxifen sensitivity. These effects were associated with decreased functional coupling between BK_Ca α and β1 subunits, but no change in total protein abundance. Overall, results suggest impairment in BK_Ca channel function in vascular smooth muscle from diabetic patients through unique mechanisms, which may contribute to vascular complications in humans with type 2 diabetes.