The KATP channel expressed in pancreatic islet β-cells is a principal homeostatic regulator of insulin secretion. Composed of four pore-forming Kir6.2 subunits and four regulatory sulfonylurea receptor 1 (SUR1) subunits, KATP channels influence the resting membrane potential, thus action potential firing, Ca2+ entry, and insulin secretion. The activity of KATP channels is dynamically regulated by glucose changes via intracellular ATP and MgADP, which bind to inhibitory and stimulatory sites to close and open the channel, respectively. This enables insulin secretion to follow fluctuations in glucose concentrations. The central role of KATP channels in insulin secretion and glucose homeostasis is underscored by dysregulated insulin secretion and blood glucose in humans bearing KATP mutations: loss-of-function mutations cause congenital hyperinsulinism characterized by persistent insulin secretion despite life-threatening hypoglycemia. Conversely, gain-of-function channel mutations result in neonatal diabetes due to insufficient insulin secretion. Here you can see a recent cryoEM structure of the rat SUR1/Kir6.2-Q52R ATP-sensitive potassium channel in an open conformation (PDB code: 8TI1)

#molecularart #potassium #channel #membrane #kir62 #atp #insulin #cryoem

Structure rendered with @proteinimaging, post-processed with @stylar.ai_official and depicted with @corelphotopaint