The therapeutic agents that target ATP-sensitive potassium channels

Abstract ATP-sensitive potassium (K ATP ) channels are a major drug target for the treatment of type-2 diabetes. K ATP channels are ubiquitously expressed and link the metabolic state to electrical excitability. In pancreatic β-cells, K ATP channels are crucial in the regulation of glucose-induced insulin secretion. Also, K ATP channels are involved in the protection against neuronal seizures and ischaemic stress in the heart, brain and in the regulation of vascular smooth muscle tone. Functional K ATP channels are hetero-octamers composed of two subunits, a pore forming Kir6, which is a member of the inwardly rectifying potassium channels family, and a regulatory sulphonylurea receptor (SUR). In response to nucleotides and pharmaceutical agonists and antagonists, SUR allosterically regulates channel gating. The allosteric communication pathways between these two heterologus proteins in K ATP channels are still poorly understood. This review will highlight the therapeutic agents that target K ATP channels and are used to treat diabetes and cardiovascular diseases.