Katp Channel

Kaxp channels under investigation resulted in selective rescue of substantia nigra dopaminergic neurons does not prove a deleterious, neurodegeneration-promoting role of Katp channels, but may simply mean that the dopamine neurons, lacking KATP channels, have developed other, undetected self-protection mechanisms. 

Key feature of KATP channels is their responsiveness to changes in intracellular ATP and ADP providing a... 

Substantia nigra pars reticulata is the area with highest neuronal activity and metabolic rate in the brain. This region also shows highest expression rates of SUR1/ Kir6.2 channels. These KATP channels are present... 

Katp channels are the targets for two classes of therapeutic agents, hypoglycaemic drugs like glibencla-mide or nateglinide and potassium channel openers like... 

Kir channels may be homo- or hetero-tetrameric complexes, in some cases in tight association with beta-subunits (e.g., the KAtp channel). 

Nichols CG (2006) KATP channels as molecular sensors of cellular metabolism. Nature 440(7083) 470-476... 

Typical KCO members are diazoxide, pinacidil, cromakalim, and nicorandil. KCOs activate KATP channels by binding to SUR subunits. Diazoxide and nicorandil are clinically used in treatment of PHHI and angina pectoris, respectively. 

SUR1 SUR1 11 p15.1 Pancreas, neurons, skeletal muscle Kir6.2 Coassemble to from KATP channels PHHI... 

Metabolic diseases In the pancreatic (3-cells, KATP channel derived from >SUR1 and Kir6.2, links cellular metabolism to electrical activity and regulates insulin secretion. Mutations in SUR1 and Kir6.2 that result in loss of Katp channel function have been identified in families with familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI). 

Mitochondria KATP channels Cardiac KATP channel opening has a role in myocardial preconditioning, a paradoxical form of cardioprotection wherein brief ischemic episodes can protect the heart from subsequent lethal ischemic injury. Openers including BMS-180448 and BMS-191095 have been reported to possess preferential cardioprotective effects over vasorelaxant effects by activating mitochondria KAXP channels. 

The approach discussed to use VolSurf derived in silica models to understand structure-PK relationships for pharmacokinetic properties was also applied to one series of selective cardiac KATP channel blockers [160]. It was found that compounds fulfilling the predefined selectivity profile exhibit only less-optimal pharmacokinetic properties because of a short plasma mean residential time (MRT). Consequently, the MRT for 28 compounds from rabbit iv studies for one series was used as dependent variable to derive a VolSurf PLS model in addition to ligand affinity SAR data. The chemical... 

The sulfonylurea receptor was identified as an adenosine triphosphate (ATP) sensitive potassium (Katp) channel that is present on the (3-cell membrane surface. Closure of these K tp channels causes (3-cell membrane... 

Akasaka T, KUnedinst S, Ocorr K, Bustamante EL, Kim SK, Bodmer R. (2006) The ATP-sensitive potassiiun (KATP) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman. Proc Natl AcadSci USA 103, 11999-2004. 

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