ATP-sensitive potassium channels

Antidiabetic Drugs other than Insulin. Figure 1 Sulphonylureas stimulate insulin release by pancreatic (3-cells. They bind to the sulphonylurea receptor (SUR-1), which closes Kir6.2 (ATP-sensitive) potassium channels. This promotes depolarisation, voltage-dependent calcium influx, and activation of calcium-sensitive proteins that control exocytotic release of insulin. 

Schwanstecher C, Schwanstecher M (2002) Nucleotide sensitivity of pancreatic ATP-sensitive potassium channels and type 2 diabetes. Diabetes 51 (Suppl 3) S358-362... 

Persistant hyperinsulinemic hypoglycemia of infancy (PHHI) SUR1 subunits of ATP-sensitive potassium channels (KATP) Sulfonylurea... 

While producing the same effect as sulfonylureas, nonsulfonylurea secretagogues, also referred to as meglitinides, have a much shorter onset and duration of action. Nonsulfonylurea secretagogues also produce a pharmacologic effect by interacting with ATP-sensitive potassium channels on the (1-cells however, this binding is to a receptor adjacent to those to which sulfonylureas bind. 

Sulfonylureas bind to a 140-kDa high-affinity sulfonylurea receptor (Figure 41-2) that is associated with a beta-cell inward rectifier ATP-sensitive potassium channel. Binding of a sulfonylurea inhibits the efflux of potassium ions through the channel and results in depolarization. Depolarization opens a voltage-gated calcium channel and results in calcium influx and the release of preformed insulin. 

Wilde AAM, Escande D, Schumacher CA, Thuringer D, Mestre M, Fiolet JWT, Janse MJ Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP-sensitive potassium channel. Circ Res 1990 67 835-843. 

Edwards, G. and Weston, A. H. The pharmacology of ATP-sensitive potassium channels, Annual Reviews Pharmacology Toxicology 1993, 33, 597-637. 

Kang, Y., Zhang, C., Qiao, J. Involvement of endogenous opioids and ATP-sensitive potassium channels in the mediation of carbachol-induced antinociception at the spinal level a behavioral study in rats, Brain Research 1997, 761, 342-346. 

Narita, M., Suzuki, T., Misawa, M., Nagase, H., Nabeshima, A., Ashizawa, T., Ozawa, H., Saito, T., Takahata, N. Role of central ATP-sensitive potassium channels in the analgesic effect and spinal noradrenaline turnover-enhancing effect of intracerebroventricularly injected morphine in mice, Brain Research 1992, 596, 209-214. 

Yang, S.-W., Kang, Y.-M., Guo, Y.-Q., Qiao J.-T. ATP-sensitive potassium channels mediate norepinephrine- and morphine-induced antinociception at the spinal cord level, International Journal Neuroscience 1998, 93, 217-223. 

Zawar, C., Plant, T. D., Schirra, C., Konnerth, A., Neumcke, B. Cell-type specific expression of ATP-sensitive potassium channels in the rat hippocampus. Journal of Physiology 1999, 514, 327-341. 

Wan TC, Ge ZD, Tampo A, Mio Y, Bienengraeber MW, Tracey WR, Gross GJ, Kwok WM, Auchampach JA (2008) The A3 adenosine receptor agonist CP-532, 903 [N6-(2, 5-dichlorobenzyl)-3 -aminoadenosine-5 -N-methylcarboxamide] protects against myocardial ischemia/reperfusion injury via the sarcolemmal ATP-sensitive potassium channel. J Pharmacol Exp Ther 324(l) 234-243... 

Headrick JP, Willems L, Ashton KJ, Holmgren K, Peart J, Matherne GP (2003) Ischaemic tolerance in aged mouse myocardium the role of adenosine and effects of A( adenosine receptor overexpression. J Physiol 549(Pt 3) 823-833 Hein TW, Belardinelli L, Kuo L (1999) Adenosine A2a receptors mediate coronary microvascular dilation to adenosine role of nitric oxide and ATP-sensitive potassium channels. J Pharmacol Exp Ther 291(2) 655-664... 

The meglitinides bind with high affinity to a site, distinct from the sulfonylurea receptor site, on the ATP-sensitive potassium channels in pancreatic beta cells and stimulate insulin secretion. After binding, the ATP-dependent potassium channels are closed, reducing potassium efflux and depolarizing the cell membrane. The meglitinides do not have to be internalized in the membrane, in contrast to the sulfonylureas. This may explain their rapid onset of... 

Dabrowski M, Wahl P, Holmes WE, Ashcroft FM. Effect of repaglinide on cloned beta cell, cardiac and smooth muscle types of ATP-sensitive potassium channels. Diabetologia 2001 44(6) 747-56. 

Sulfonylureas act by inhibiting ATP-sensitive potassium channels (KAtp channels) in pancreatic beta cells, increasing the amount of insulin released. The beta cells... 

Baek WK, Jang BC, Lim JH, Kwon TK, Lee HY, Cho CH, Kim DK, Shin DH, Park JG, Lim JG, Bae JH, Yoo SK, Park WK, Song DK. 2005. Inhibitory modulation of ATP-sensitive potassium channels by gallate-ester moiety of (—)-epigallocatechin-3-gallate. Biochem Pharmacol 70 1560-1567. 

INDUCTION BY SELEGILINE OF DOPAMINE RELEASE THROUGH AN ATP-SENSITIVE POTASSIUM CHANNEL... 

CPZ (9), triflupromazine (11), and fluphenazine (3) inhibited HIT-T15 pancreatic (3-cell ATP-sensitive potassium channels in a dose-dependent manner [254], Reversible inhibition of these channels was observed when they were activated by ATP depletion or by treatment with the channel opener diazoxide. The IC50 values for CPZ (9), triflupromazine (11), and fluphenazine (3) were 1, 4, and 6 xM, respectively. 

Woodfork KA, Wonderlin WF, Peterson VA, Strobl JS (1995) Inhibition of ATP-sensitive potassium channels causes reversible cell-cycle arrest of human breast cancer cells in tissue culture. J Cell Physiol 162 163-171... 

Although repaglinide [reh PAG lih nide] is not a sulfonylurea, it has actions in common with this group of drugs. Repaglinide binds to the ATP-sensitive potassium channels of the pancreatic (3 cells, causing the release of insulin. Repaglinide is well absorbed orally, and is taken three times a day before meals (its ti/2 = 1 hr). 

It also has an effect on ATP-sensitive potassium channels in glucose-responsive neurones, which affect the neuronal firing rate. Leptin has major effects on reproductive behaviour (sexual maturation is delayed by lack of food). Starving women, female athletes and anorexics with low fat stores experience secondary amenorrhea. Leptin signalling defects lead to gross obesity, but these are very rare in humans. 

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