ABSTRACT

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.

摘要

线粒体 BK _Ca通道 (mitoBK _Ca ) 是质膜 BK _Ca (Maxi-K、BK _Ca、Slo1、K _Ca 1.1)的剪接变体。虽然 mitoBK _Ca的高分辨率结构尚不可用，但质膜 BK _{Ca 的}功能和结构研究为电压和 Ca ²⁺通道门控以及与辅助亚基的相互作用提供了重要线索。迄今为止，我们知道 mitoBK _Ca表达的控制、靶向和电压敏感性很大程度上取决于其与其调节性 β1 亚基的关联，后者总体上参与了线粒体 Ca 的控制^{2+ -}心肌细胞超负荷。此外，最近提出了 mitoBK _{Ca 的}新调节机制，例如 β-亚基和淀粉样蛋白-β。然而，包括调节性 BK _Ca -β1-亚基如何到达线粒体以及淀粉样蛋白-β 损害 mitoBK _Ca通道功能的机制等主要基本问题仍有待解决。