Regulatory mechanisms of mitochondrial BK(Ca) channels

The mitochondrial BK(Ca) channel (mitoBK(Ca)) is a splice variant of plasma membrane BK(Ca) (Maxi-K, BK(Ca), Slo1, K(Ca)1.1). 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 Ca(2+), 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 Ca(2+)-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.