ATP-sensitive inward rectifier potassium channel 6.2 (KCNJ11) (KCNJ11)

The ATP-sensitive inward rectifier potassium channel 6.2 (Kir6.2) is a critical protein encoded by the KCNJ11 gene that forms the pore-forming subunit of the ATP-sensitive potassium (KATP) channel. In pancreatic beta cells, Kir6.2 associates with the regulatory sulfonylurea receptor 1 (SUR1) to regulate insulin secretion in response to blood glucose levels (UniProt P48549). When intracellular ATP levels rise due to glucose metabolism, the Kir6.2 channel closes, leading to membrane depolarization, the opening of voltage-gated calcium channels, and the subsequent release of insulin (PubMed: 15917854). Mutations in the KCNJ11 gene are linked to clinical conditions such as neonatal diabetes mellitus and congenital hyperinsulinism (NIH: GeneReviews). Therapeutically, Kir6.2 is the primary target for sulfonylurea drugs, which promote insulin release by inducing channel closure, and diazoxide, which keeps the channel open to treat hypoglycemia (StatPearls: Sulfonylureas). This channel also plays roles in other tissues, including the heart and brain, where it helps protect cells against metabolic stress (PubMed: 11566915).

Other names

Kir6.2BIRHHF2TNDM3PHHIMODY13Potassium channel, inwardly rectifying subfamily J member 11KCNJ11

Sulfonylureas and meglitinides inhibit the channel to stimulate insulin secretion, while diazoxide activates the channel to inhibit insulin release.