Mitochondrial Ca2+-activated K+ channels and their role in cell life and death pathways

Mitochondrial calcium mito[Ca2+] influx occurs via the voltage-dependent anion channel (VDAC) at the outer mitochondrial membrane (OMM) and the mitochondrial calcium uniporter (MCU) at the inner mitochondrial membrane (IMM). Potassium (K+) influx via the mitoKCa channels attenuates the loss of the mitochondrial membrane potential, thereby reducing the mito[Ca2+] and ROS production.▪ •Mitochondrial potassium channel activation mediated neuroprotection and cardioprotection.•Mitochondrial potassium channels are associated with preconditioning-mediated protection.•Mitochondrial calcium uptake is regulated by mitochondrial potassium channels. Ca2+-activated K+ channels (KCa) are expressed at the plasma membrane and in cellular organelles. Expression of all KCa channel subtypes (BK, IK and SK) has been detected at the inner mitochondrial membrane of several cell types. Primary functions of these mitochondrial KCa channels include the regulation of mitochondrial ROS production, maintenance of the mitochondrial membrane potential and preservation of mitochondrial calcium homeostasis. These channels are therefore thought to contribute to cellular protection against oxidative stress through mitochondrial mechanisms of preconditioning. In this review, we summarize the current knowledge on mitochondrial KCa channels, and their role in mitochondrial function in relation to cell death and survival pathways. More specifically, we systematically discuss studies on the role of these mitochondrial KCa channels in pharmacological preconditioning, and according protective effects on ischemic insults to the brain and the heart.