ATP-sensitive K+ (KATP) channels are present in a wide variety of tissues. The sensitivity of these channels to closure by cytosolic ATP (ATPi) varies significantly among different tissues and even within the same tissue. The purpose of this study was to test the hypothesis that negative surface charges modulate the sensitivity of the KATP channels to ATPi by influencing surface potential in th...

Existing concepts and models for glucose-stimulated insulin secretion (GSIS) are overviewed and a newer perspective has been formulated toward the physiological understanding of GSIS. A conventional model has been created on the basis of in vitro data on application of a square wave high glucose in the absence of any other stimulatory inputs. Glucose elicits rapid insulin release through an ade...

BACKGROUND AND PURPOSE The 2-propyl-1,4 benzoxazine (AM10) shows a peculiar behaviour in skeletal muscle, inhibiting or opening the ATP-sensitive K(+) (KATP) channel in the absence and presence of ATP, respectively. We focused on tissue selectivity and mechanism of action of AM10 by testing its effects on pancreatic KATP channels by means of both in vitro and in vivo investigations. EXPERIMEN...

Pék-Scott, Marta, and Peter L. Lutz. ATP-sensitive K1 channel activation provides transient protection to the anoxic turtle brain. Am. J. Physiol. 275 (Regulatory Integrative Comp. Physiol. 44): R2023–R2027, 1998.—There is wide speculation that ATP-sensitive K1 (KATP) channels serve a protective function in the mammalian brain, being activated during periods of energy failure. The aim of the pr...

BACKGROUND We reported that digoxin abolishes the infarct size (IS)-limiting effect of ischemic preconditioning (IPC). Because ATP-sensitive K+ (KATP) channels are involved in IPC, we studied whether Na+,K+-ATPase and KATP channels functionally interact, thereby modulating IPC. METHODS AND RESULTS Rabbits received 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. IPC...

The ATP-sensitive K+ (KATP) channel, composed of Kir6.2 and sulfonylurea receptor (SUR1), in pancreatic beta-cells is believed to serve as a metabolic sensor regulating insulin secretion according to glucose levels. Thus, genetic disruption of Kir6.2 expression may impair KATP channel function in glucose sensing and insulin secretion. Here we show evidence obtained from functional genetic assay...

Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic KATP channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides. Here, we present a cryo-EM structure of the channel bound to a high-affinity sulfonylurea drug glibenclami...

ATP sensitive potassium (KATP) channels are metabolic sensors with channel activity promoted by decreases in ATP andnor increases in MgADP. The most studied are channels present in cardiac myocytes and pancreatic b cells but KATP currents also exist more widely in a range of tissues and organs [1,2]. The channel is a hetero-octamer comprising four sulphonylurea receptors and four pore-forming i...

BACKGROUND ATP-sensitive potassium (KATP) channels in neurons regulate excitability, neurotransmitter release and mediate protection from cell-death. Furthermore, activation of KATP channels is suppressed in DRG neurons after painful-like nerve injury. NO-dependent mechanisms modulate both KATP channels and participate in the pathophysiology and pharmacology of neuropathic pain. Therefore, we i...

ATP-sensitive inwardly rectifying potassium channels are expressed in a variety of tissues, including heart, skeletal, and smooth muscle, and pancreatic beta-cells. Physiological and pharmacological studies suggest the presence of distinct KATP channels in these tissues. Recently, the KATP channel of beta-cells has been reconstituted in functional form by coexpression of SUR, the sulfonylurea-b...