1. The patch-clamp technique has been used to examine the action of the chemical phosphatase 2,3-butanedione monoxime (BDM) on ATP-sensitive K+ channels (KATP-channels) from mouse isolated pancreatic beta-cells in the absence of ATP and Mg2+. 2. BDM reversibly inhibited whole-cell KATP-currents with a concentration for half maximal inhibition (K(i)) of 15 +/- 1 mM and a Hill coefficient (n) of ...

Closure of ATP-sensitive K+ channels (KATP channels) is a key step in glucose-stimulated insulin secretion. The precise mechanism(s) by which glucose metabolism regulates KATP channel activity, however, remains controversial. It is widely believed that the principal determinants are the intracellular concentrations of the metabolic ligands, ATP and ADP, which have opposing actions on KATP chann...

THE DISCOVERY AND CHARACTERIZATION OF preconditioning (PC) in the late 1980s has proven to be the most important advancement in the pursuit to identify viable strategies to limit infarct size following myocardial ischemia-reperfusion injury. Ischemic PC (IPC) is a unique, paradoxical phenomenon whereby one or several short intermittent periods of ischemia protects tissue against the injury caus...

The ATP-sensitive K+ (KATP) channel controls blood glucose levels by coupling metabolism to insulin secretion in pancreatic β-cells. E23K, a common polymorphism the pore-forming KATP subunit (KCNJ11) gene, has been linked increased risk of type 2 diabetes. Understanding risk-allele-specific pathogenesis potential improve personalized diabetes treatment, but underlying mechanism remained elusive...

ATP-sensitive K+ (KATP) channels play a regulatory role in hormone-secreting pancreatic islet α-, β- and δ-cells. Targeted channel deletion would assist analysis and dissection of the intraislet regulatory network. Toward this end Abcc8/Sur1 flox mice were generated and tested by crossing with glucagon-(GCG)-cre mice to target α-cell KATP channels selectively. Agonist resistance was used to qua...

ATP-sensitive potassium (KATP) channels in striated myocytes are heteromultimers of KIR6.2, a weak potassium inward rectifier, plus SUR2A, a low-affinity sulfonylurea receptor. We have cloned human KIR6.2 (huKIR6.2) and a huSUR2A that corresponds to the major, full-length splice variant identified by polymerase chain reaction analysis of human cardiac poly A+ mRNA. ATP- and glibenclamide-sensit...

ATP-sensitive K (KATP) channels are nucleotide-gated bioenergy sensors that enable high-fidelity feedback communication between cellular energy dynamics and membrane electric activity.1–4 Particularly dense in cardiac sarcolemma where they are composed through heteromultimeric assembly of inwardly rectifying K channel pores, typically KCNJ11-encoded Kir6.2 proteins, and regulatory ATPbinding ca...

The ATP-sensitive potassium (KATP) channel in pancreatic islet beta cells consists of four pore-forming (Kir6.2) subunits and four regulatory sulfonylurea receptor (SUR1) subunits. In beta cells, the KATP channel links intracellular metabolism to the dynamic regulation of the cell membrane potential that triggers insulin secretion. Syntaxin 1A (Syn-1A) is a SNARE protein that not only plays a d...

Duncker, D. J., H. H. Oei, F. Hu, R. Stubenitsky, and P. D. Verdouw. Role of KATP 1 channels in regulation of systemic, pulmonary, and coronary vasomotor tone in exercising swine. Am J Physiol Heart Circ Physiol 280: H22–H33, 2001.—The role of ATP-sensitive K (KATP 1 ) channels in vasomotor tone regulation during metabolic stimulation is incompletely understood. Consequently, we studied the con...

It has been previously shown that hyperlipidemia interferes with cardioprotective mechanisms. Here, we investigated the interaction of hyperlipidemia with cardioprotection induced by pharmacological activators of ATP-sensitive K(+) (KATP) channels. Hearts isolated from rats fed a 2% cholesterol-enriched diet or normal diet for 8 wk were subjected to 30 min of global ischemia and 120 min of repe...