Functional regulation of large conductance Ca²⁺-activated K⁺ channels in vascular diseases

The large conductance Ca²⁺-activated potassium channels, the BK channels, is widely expressed in various tissues and activated in a Ca²⁺- and voltage-dependent manner. The activation of BK channels hyperpolarizes vascular smooth muscle cell membrane potential, resulting in vasodilation. Under pathophysiological conditions, such as diabetes mellitus and hypertension, impaired BK channel function exacerbates vascular vasodilation and leads to organ ischemia. The vascular BK channel is composed of 4 pore-forming subunits, BK-α together with 4 auxiliary subunits: β₁ subunits (BK-β₁) or γ₁ subunits (BK-γ₁). Recent studies have shown that down-regulation of the BK β₁ subunit in diabetes mellitus induced vascular dysfunction; however, the molecular mechanism of these vascular diseases is not well understood. In this review, we summarize the potential mechanisms regarding BK channelopathy and the potential therapeutic targets of BK channels for vascular diseases.