Regulatory mechanisms of mitochondrial BKCa channels.

The mitochondrial BK_Ca channel (mitoBK_Ca) is a splice variant of plasma membrane BK_Ca (Maxi-K, BK_Ca, Slo1, K_Ca1.1). While a high-resolution structure of mitoBK_Ca is not available yet, functional and structural studies of the plasma membrane BK_Ca have provided important clues on the gating of the channel by voltage and Ca²⁺, as well as the interaction with auxiliary subunits. To date, we know that the control of expression of mitoBK_Ca, targeting and voltage-sensitivity strongly depends on its association with its regulatory β1-subunit, which overall participate in the control of mitochondrial Ca²⁺-overload in cardiac myocytes. Moreover, novel regulatory mechanisms of mitoBK_Ca such as β-subunits and amyloid-β have recently been proposed. However, major basic questions including how the regulatory BK_Ca-β1-subunit reaches mitochondria and the mechanism through which amyloid-β impairs mitoBK_Ca channel function remain to be addressed.