Cardiac mitochondrial ATP-sensitive potassium channel (mitoKATP) (mitoKATP)

The cardiac mitochondrial ATP-sensitive potassium channel (mitoKATP) is a critical protein complex located in the inner mitochondrial membrane that plays a pivotal role in cardioprotection and mitochondrial volume regulation. It is a primary mediator of ischemic preconditioning, a phenomenon where brief, non-lethal periods of ischemia protect the heart against subsequent severe ischemic injury (O'Rourke, 2004; PubMed: 15082356). The molecular identity of mitoKATP was recently identified as a complex consisting of the pore-forming subunit CCDC51 (MITOK) and the regulatory subunit ABCB8 (MITOSUR) (Paggio et al., 2019; Nature: 572(7771)). Activation of the channel by pharmacological agents like diazoxide leads to potassium influx into the mitochondrial matrix, causing mild membrane depolarization and the release of signaling reactive oxygen species (ROS) (Garlid & Halestrap, 2012; PubMed: 22227311). These ROS act as secondary messengers to activate survival signaling pathways that inhibit the opening of the mitochondrial permeability transition pore (mPTP), preventing cardiomyocyte death. While mitoKATP is a highly attractive therapeutic target for myocardial infarction and heart failure, achieving drug selectivity to avoid off-target effects on sarcolemmal and pancreatic KATP channels remains a significant challenge in drug development.

Other names

Mitochondrial ATP-sensitive potassium channelmitoKATP channelCCDC51/ABCB8 complexMITOK/MITOSUR complex

Opening of the channel facilitates potassium ion entry into the mitochondrial matrix, causing mild depolarization and ROS-mediated signaling that prevents mitochondrial permeability transition pore (mPTP) opening.