Membrane trafficking of large conductance Ca²⁺- and voltage-activated K⁺ (BK) channels is regulated by Rab4 GTPase

The large conductance voltage- and Ca2+ activated K+ (BK) channel is a major ionic determinant of vascular tone, vasodilation, and blood pressure. The activity of BK channels is regulated in part by membrane presentation. Rab GTPase (Rab) regulates important cellular processes, including ion channel membrane trafficking. We hypothesize that Rab4a participates in the regulation of BK channel alpha-subunit (BK-alpha) membrane trafficking. We found that vascular BK-alpha interacts physically with Rab4a. Co-expression of dominant-negative Rab4a reduced BK-alpha surface expression, whereas that of constitutively-active Rab4a augmented BK-alpha surface presentation. These novel findings suggest that vascular BK channel membrane expression is regulated by Rab4a through channel membrane trafficking.