Targeting Microglial K_ATP Channels to Treat Neurodegenerative Diseases: A Mitochondrial Issue

Figure 3

Diazoxide modifies microglial reactivity in the brain. Drawing of the effects of mitochondrial K_ATP (mitoK_ATP) channel opening in the energy metabolism and its consequences in the microglia reaction during neurodegeneration. (1) Diazoxide activates mitoK_ATP channels, which (2) depolarizes the mitochondrial internal membrane (MIM), and (3) induces translocation of H⁺ by the electron transport chain (ETC) that enhances both ATP synthesis and activation of the mitochondrial calcium uniporter (MCU) (4). Calcium in the mitochondria activates dehydrogenases of the tricarboxylic acid cycle (TCA) (5) that also enhances ATP production (6). ATP closes the K_ATP channel from the plasma membrane (7), while diazoxide opens the channel. As a result, the cell response to activation signals decreases (8), leading to a reduction of the ROS generation and the inflammatory response (9) of reactive microglia (see the text for details).