A VIEW OF SUR/KIR6.X, KATP CHANNELS
Tóm tắt
▪ Abstract ATP-sensitive potassium channels, termed KATP channels, link the electrical activity of cell membranes to cellular metabolism. These channels are heteromultimers of sulfonylurea receptor (SUR) and KIR6.x subunits associated with a 1:1 stoichiometry as a tetramer (SUR/KIR6.x)4. KIR6.x forms the pores, whereas SUR regulates their activity. Changes in [ATP]i and [ADP]i gate the channel. The diversity of KATP channels results from the assembly of SUR and KIR6.x subtypes. KIR6.1-based channels differ from KIR6.2 channels mainly by their smaller unitary conductance. SUR1- and SUR2-based channels are distinguished by their differential sensitivity to sulfonylureas, whereas SUR2A-based channels are distinguished from SUR2B channels by their differential sensitivity to diazoxide. Mutations that result in the loss of KATP channels in pancreatic β-cells have been identified in SUR1 and KIR6.2. These mutations lead to familial hyperinsulinism. Understanding the mutations in SUR and KIR6.x is allowing insight into how these channels respond to nucleotides, sulfonylureas, and potassium channel openers, KCOs.
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Tài liệu tham khảo
Carmeliet E, Storms L, Vereecke Y. 1990. The ATP-dependent K-channel and metabolic inhibition. InCardiac Electrophysiology. From Cell to Bedside, ed. DP Zipes, Yalife, pp. 103–8. Philadelphia: Saunders
Babenko AP, 1992, Basic Appl. Myology, 2, 316
Aguilar-Bryan L, 1996, Diabetes Rev., 4, 336
Gopalakrishnan M, 1991, J. Pharmacol. Exp. Therapeut., 257, 1162
Gehlert DR, 1991, J. Pharmacol. Exp. Therapeut., 257, 901
Aguilar-Bryan L, 1997, Meth. Enzymol.
Kajioka S, 1990, J. Pharmacol. Exp. Therapeut., 254, 905
Kamouchi M, 1994, Am. J. Physiol., 266, H1687
Kovacs RJ, 1991, Am. J. Physiol., 261, H604
Murphy E, 1993, Miner. Electrolyte Metab., 19, 250
Kirsch GE, 1990, Am. J. Physiol., 259, H820
Permutt MA, 1996, Diabetes Rev., 4, 347
Arena JP, 1989, Am. J. Physiol., 257, H2092
Thuringer D, 1989, Mol. Pharmacol., 36, 897