ATP‐Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles

Abstract

ATP sensitive potassium channels (K ) are so named because they open as cellular ATP levels fall. This leads to membrane hyperpolarization and thus links cellular metabolism to membrane excitability. They also respond to MgADP and are regulated by a number of cell signaling pathways. They have a rich and diverse pharmacology with a number of agents acting as specific inhibitors and activators. K channels are formed of pore-forming subunits, Kir6.1 and Kir6.2, and a large auxiliary subunit, the sulfonylurea receptor (SUR1, SUR2A, and SUR2B). The Kir6.0 subunits are a member of the inwardly rectifying family of potassium channels and the sulfonylurea receptor is part of the ATP-binding cassette family of proteins. Four SURs and four Kir6.x form an octameric channel complex and the association of a particular SUR with a specific Kir6.x subunit constitutes the K current in a particular tissue. A combination of mutagenesis work combined with structural studies has identified how these channels work as molecular machines. They have a variety of physiological roles including controlling the release of insulin from pancreatic β cells and regulating blood vessel tone and blood pressure. Furthermore, mutations in the genes underlie human diseases such as congenital diabetes and hyperinsulinism. Additionally, opening of these channels is protective in a number of pathological conditions such as myocardial ischemia and stroke. © 2018 American Physiological Society. Compr Physiol 8:1463-1511, 2018.

Distinct signatures of calcium activity in brain pericytes

“…Figure 5D). (Dart and Standen, 1995, Tinker et al, 2018, Reiner et al, 1990, Lerchundi et al, 2019. Indeed, CP calcium signals decreased in response to NaN3 (baseline, S: 9.4 (4.6), P: 32.3 (10.2); NaN3, S: 0.3 (0.8), P: 4.6 (5.0).…”

Handling of Ventricular Fibrillation in the Emergency Setting

“…ATP-sensitive potassium channels (K ATP channels) localized in the sarcolemmal membrane may be activated by metabolic stress or ischemia causing the shortening of APD, preventing the heart from calcium overload and contraction abnormalities. Moreover, myocardial hypertrophy and ischemia can increase the expression levels of Kir 6.1 and Kir 6.2 K ATP channels, leading to an increased risk for ventricular dysrhythmias based on heterogeneous shortening of the AP (Akrouh et al, 2009;Tinker et al, 2018). In 1998 repolarization reserve has been defined by Roden et al as a defensive mechanism of the myocardium, which protects the heart from the emergence of arrhythmias in particular circumstances where APD has already been prolonged.…”

Ion Transporters, channelopathies, and glucose disorders

“…K ATP channels, members of the inwardly rectifying potassium channel family, are large octameric complexes which permit the flux of potassium ions across the cell membrane [12][13][14][15]. They are composed of four pore-forming subunits (Kir6.1 or Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and four regulatory sulphonylurea receptors (SUR1, SUR2A or SUR2B) which are encoded by ATP-binding cassette subfamily C member 8 (ABCC8) [13][14][15].…”