Acta Pharm. 66 (2016) 23-34

full paper

Review

The therapeutic agents that target ATP-sensitive potassium channels

HUSSEIN N. RUBAIY

h.rubaiy@leeds.ac.uk

School of Medicine, The Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Building 7.27, University of Leeds, U.K.

Accepted September 15, 2015

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.

Keywords: ATP-sensitive potassium channels, therapeutic agents, diabetes, cardiovascular, inwardly rectifying potassium channels, sulphonylurea receptor