Small-molecule modulators of inward rectifier K+ channels: Recent advances and future possibilities

Future Medicinal Chemistry

Volumn 2, Issue 5, 2010, Pages 757-774

  Bhave, Gautam ^a   Lonergan, Daniel ^a   Chauder, Brian A ^a   Denton, Jerod S ^a,b  

^a VANDERBILT UNIVERSITY   (United States)

^b Vanderbilt Digestive Disease Research Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2' (4 METHOXYPHENYLACETAMIDOMETHYL) N [2 (3 PYRIDYL)ETHYL] 2 BIPHENYLCARBOXAMIDE; 3 BICYCLO[2.2.1]HEPT 2 YL BENZENE 1,2 DIOL; 3,4 DICHLORO N METHYL N [2 (1 PYRROLIDINYL)CYCLOHEXYL]BENZENEACETAMIDE METHANESULFONATE; 4 [3 (4 BENZYL 1 PIPERIDINYL)PROPIONYL] 2,3,4,5 TETRAHYDRO 7 METHOXY 1,4 BENZOTHIAZEPINE; 8 CHLORO 2,3,4,5 TETRAHYDRO 3 METHYL 5 PHENYL 1H 3 BENZAZEPIN 7 OL HYDROGEN MALEATE; ANTIARRHYTHMIC AGENT; BENZENE DERIVATIVE; BUMETANIDE; CELASTROL; CHLOROETHYLCLONIDINE; CHLOROQUINE; DEXTROPROPOXYPHENE; DIPHENHYDRAMINE; ETHOSUXIMIDE; FLUOXETINE; FUROSEMIDE; GAMBOGIC ACID; INWARDLY RECTIFYING POTASSIUM CHANNEL; INWARDLY RECTIFYING POTASSIUM CHANNEL SUBUNIT KIR1.1; INWARDLY RECTIFYING POTASSIUM CHANNEL SUBUNIT KIR2.1; MEPYRAMINE; NARCOTIC ANALGESIC AGENT; NORTRIPTYLINE; PROTEIN INHIBITOR; TAMOXIFEN; THIORIDAZINE; TORASEMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERNAKALANT; VU 590;

DRUG TARGETING; HEART ARRHYTHMIA; HUMAN; HYPERTENSION; NONHUMAN; PAIN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; UNSPECIFIED SIDE EFFECT;

ANIMALS; DRUG DISCOVERY; HUMANS; MODELS, MOLECULAR; POTASSIUM CHANNELS, INWARDLY RECTIFYING; SMALL MOLECULE LIBRARIES;

EID: 77953405501     PISSN: 17568919     EISSN: None     Source Type: Journal    
DOI: 10.4155/fmc.10.179     Document Type: Review

References (116)

1. Nichols CG, Lopatin AN. Inward rectifier potassium channels. Annu. Rev. Physiol. 59, 171-191 (1997).
2. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol. Rev. 90 (1), 291-366 (2010). □ Most recent extensive review of the Kir channel family.
3. Ho K, Nichols CG, Lederer WJ et al. Cloning and expression of an inwardly rectifying ATP-regulated potassium channel. Nature 362 (6415), 31-38 (1993). □ Describes the cloning and functional properties of the first member of the Kir channel family, renal outer medullary first (ROMK).
4. Lopatin AN, Makhina EN, Nichols CG. Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification. Nature 372, 366-369 (1994).
5. + channels. Annu. Rev. Physiol. 66, 103-129 (2004).
6. Kuo A, Gulbis JM, Antcliff JF et al. Crystal structure of the potassium channel KirBac1.1 in the closed state. Science 300 (5627), 1922-1926 (2003). □ Describes the first crystal structure of a full-length bacterial Kir channel.
7. Pegan S, Arrabit C, Zhou W et al. Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification. Nat. Neurosci. 8 (3), 279-287 (2005).
8. Nishida M, Cadene M, Chait BT, MacKinnon R. Crystal structure of a Kir3.1-prokaryotic Kir channel chimera. EMBO. J. 26 (17), 4005-4015 (2007).
9. Nishida M, MacKinnon R. Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 a resolution. Cell 111 (7), 957-965 (2002).
10. Tao X, Avalos JL, Chen J, MacKinnon R. Crystal structure of the eukaryotic strong inward-rectifier first channel Kir2.2 at 3.1 A resolution. Science 326 (5960), 1668-1674 (2009). □ Describes the first crystal structure of a full-length eukaryotic Kir channel.
11. Fallen K, Banerjee S, Sheehan J et al. The Kir channel immunoglobulin domain is essential for Kir1.1 (ROMK) thermodynamic stability, trafficking and gating. Channels (Austin) 3 (1), 57-68 (2009).
12. Rapedius M, Fowler PW, Shang L, Sansom MS, Tucker SJ, Baukrowitz T. H bonding at the helix-bundle crossing controls gating in Kir potassium channels. Neuron 55 (4), 602-614 (2007).
13. Rodriguez-Menchaca AA, Navarro-Polanco RA, Ferrer-Villada T et al. The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel. Proc. Natl Acad. Sci. USA 105 (4), 1364-1368 (2008). Exemplary study delineating the mechanism of chloroquine block of Kir2.1 using electrophysiology, mutagenesis and molecular modeling.
14. Furutani K, Ohno Y, Inanobe A, Hibino H, Kurachi Y. Mutational and in silico analyses for antidepressant block of astroglial inwardrectifer Kir4.1 channel. Mol. Pharmacol. 75 (6), 1287-1295 (2009). Exemplary study delineating the mechanism of antidepressant block of Kir4.1 using electrophysiology, mutagenesis and molecular odeling.
15. + channel activity in the nephron.
16. Hebert SC, Friedman PA, Andreoli TE. Effects of antidiuretic hormone on cellular conductive pathways in mouse medullary thick ascending limbs of Henle: I. ADH increases transcellular conductance pathways. J. Membr. Biol. 80 (3), 201-219 (1984).
17. - absorption. J. Membr. Biol. 80 (3), 221-233 (1984).
18. - and Na-Cl cotransporters and ROMK potassium channels in urinary concentrating mechanism. Am. J. Physiol. (44), 275, F325-F327 (1998).
19. Frindt G, Shah A, Edvinsson J, Palmer LG. Dietary K regulates ROMK channels in connecting tubule and cortical collecting duct of rat kidney. Am. J. Physiol. Renal Physiol. 296 (2), F347-F354 (2009).
20. +) handling in the renal collecting duct. Pflugers Arch. 458 (1), 157-168 (2009).
21. + channel, ROMK. Nat. Genet. 14 (2), 152-156 (1996).
22. Seyberth HW. An improved terminology and classification of Bartter-like syndromes. Nat. Clin. Pract. Nephrol. 4 (10), 560-567 (2008).
23. Peters M, Ermert S, Jeck N et al. Classification and rescue of ROMK mutations underlying hyperprostaglandin E syndrome/antenatal Bartter syndrome. Kidney Int. 64 (3), 923-932 (2003).
24. Schulte U, Hahn H, Konrad M et al. pH gating of ROMK (Kir1.1) channels: control by an Arg-Lys-Arg triad disrupted in antenatal Bartter syndrome. Proc. Natl Acad. Sci. USA 96 (26), 15298-15303 (1999).
25. Flagg TP, Tate M, Merot J, Welling PA. A mutation linked with Bartter's syndrome locks Kir 1.1a (ROMK1) channels in a closed state. J. Gen. Physiol. 114 (5), 685-700 (1999).
26. Good DW, Wright FS. Luminal influences on potassium secretion: sodium concentration and fluid flow rate. Am. J. Physiol. 236 (2), F192-F205 (1979).
27. Khanna A, Kurtzman NA. Metabolic alkalosis. J. Nephrol. 19 (Suppl. 9), S86-S96 (2006).
28. Sansom SC, Welling PA. Two channels for one job. Kidney Int. 72 (5), 529-530 (2007).
29. Rodan AR, Huang CL. Distal potassium handling based on flow modulation of maxi-K channel activity. Curr. Opin. Nephrol. Hypertens. 18 (4), 350-355 (2009).
30. Grimm PR, Sansom SC. BK channels in the kidney. Curr. Opin. Nephrol. Hypertens. 16 (5), 430-436 (2007).
31. - cotransporter NKCC2. Nat. Genet. 13 (2), 183-188 (1996).
32. Hebert SC. Bartter syndrome. Curr. Opin. Nephrol. Hypertens. 12 (5), 527-532 (2003).
33. Bailey MA, Cantone A, Yan Q et al. Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter's syndrome and in adaptation to a high-K diet. Kidney Int. 70 (1), 51-59 (2006).
34. Ji W, Foo JN, O'Roak BJ et al. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat. Genet. 40 (5), 592-599 (2008). Reports that heterozygous carriers of KCNJ1 loss-of-function mutations have lower blood pressure, but not pathological derangement of kidney function observed in Bartter syndrome.
35. +.
36. Brater DC. Diuretic therapy. N. Engl. J. Med. 339 (6), 387-395 (1998).
37. Grobbee DE, Hoes AW. Non-potassiumsparing diuretics and risk of sudden cardiac death. J. Hypertens. 13 (12 Pt 2), 1539-1545 (1995).
38. Macdonald JE, Struthers AD. What is the optimal serum potassium level in cardiovascular patients? J. Am. Coll. Cardiol. 43 (2), 155-161 (2004).
39. + channel function.
40. C2 channel blockers. Bioorg. Med. Chem. Lett. 18 (20), 5694-5697 (2008).
41. Gentles RG, Grant-Young K, Hu S et al. Initial SAR studies on apamin-displacing 2-aminothiazole blockers of calcium-activated small conductance potassium channels. Bioorg. Med. Chem. Lett. 18 (19), 5316-5319 (2008).
42. Titus SA, Beacham D, Shahane SA et al. A new homogeneous high-throughput screening assay for profiling compound activity on the human ether-a-go-go-related gene channel. Anal. Biochem. 394 (1), 30-38 (2009).
43. - cotransporter.
44. Nadeau H, McKinney S, Anderson DJ, Lester HA. ROMK1 (Kir1.1) causes apoptosis and chronic silencing of hippocampal neurons. J. Neurophysiol. 84 (2), 1062-1075 (2000).
45. Yoo D, Fang L, Mason A, Kim BY, Welling PA. A phosphorylation-dependent export structure in ROMK (Kir1.1) channel overrides an endoplasmic reticulum localization signal. J. Biol. Chem. 280 (42), 35281-35289 (2005).
46. + channel (ROMK). Proc. Natl Acad. Sci. USA 102 (28), 9954-9959 (2005).
47. Lewis LM, Bhave G, Chauder BA et al. High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1. Mol. Pharmacol. 76 (5), 1094-1103 (2009). □□ Describes the first high-throughput screen for modulators of Kir1.1 and the identification of the first small-molecule Kir1.1 and Kir7.1 channel inhibitor, VU590.
48. + channel with unique pore properties. Neuron 20 (5), 995-1005 (1998).
49. Ookata K, Tojo A, Suzuki Y et al. Localization of inward rectifier potassium channel Kir7.1 in the basolateral membrane of distal nephron and collecting duct. J. Am. Soc. Nephrol. 11 (11), 1987-1994 (2000).
50. Yang D, Zhang X, Hughes BA. Expression of inwardly rectifying potassium channel subunits in native human retinal pigment epithelium. Exp. Eye Res. 87 (3), 176-183 (2008).
51. +-ATPase. Biochem. J. 342 (Pt 2), 329-336 (1999).
52. + channels is caused by intracellular spermine. Cell 80 (1), 149-154 (1995).
53. + channel. Nature 371 (6494), 243-246 (1994).
54. + channels localized to a single negatively charged residue. Nature 371 (6494), 246-249 (1994).
55. + channel block by the polyamine spermine. J. Gen. Physiol. 125 (4), 413-426 (2005).
56. Plaster NM, Tawil R, Tristani-Firouzi M et al. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 105 (4), 511-519 (2001).
57. Ehrlich JR. Inward rectifier potassium currents as a target for atrial fibrillation therapy. J. Cardiovasc. Pharmacol. 52 (2), 129-135 (2008).
58. + channel inhibitor identified by high-throughput screening in yeast. Mol. Pharmacol. 65 (1), 214-219 (2004). □ Describes a high-throughput assay of mammalian Kir2.1 expressed in yeast.
59. + channel by gambogic acid. J. Biol. Chem. 284 (23), 15432-15438 (2009).
60. Sun H, Shikano S, Xiong Q, Li M. Function recovery after chemobleaching (FRAC): evidence for activity silent membrane receptors on cell surface. Proc. Natl Acad. Sci. USA 101 (48), 16964-16969 (2004).
61. Sun H, Liu X, Xiong Q, Shikano S, Li M. Chronic inhibition of cardiac Kir2.1 and hERG potassium channels by celastrol with dual effects on both ion conductivity and protein trafficking. J. Biol. Chem. 281 (9), 5877-5884 (2006).
62. + channels by chloroethylclonidine. Br. J. Pharmacol. 128 (3), 760-766 (1999).
63. Liu B, Jia Z, Geng X et al. Selective inhibition of Kir currents by antihistamines. Eur. J. Pharmacol. 558 (1-3), 21-26 (2007).
64. + 2.x family of inward rectifier channels by interfering with phosphatidylinositol 4, 5-bisphosphate-channel interactions. J. Pharmacol. Exp. Ther. 331 (2), 563-573 (2009).
65. + channel Kir2.3. PLoS One 4 (7), E6311 (2009).
66. Sadja R, Alagem N, Reuveny E. Gating of GIRK channels. details of an intricate, membrane-delimited signaling complex. Neuron 39 (1), 9-12 (2003).
67. +-channel proteins. Nature 374 (6518), 135-141 (1995).
68. Koyrakh L, Lujan R, Colon J et al. Molecular and cellular diversity of neuronal G proteingated potassium channels. J. Neurosci. 25 (49), 11468-11478 (2005).
69. + channels. Eur. J. Biochem. 267 (19), 5830-5836 (2000).
70. B receptor agonists on the mesolimbic dopamine system. Nat. Neurosci. 7 (2), 153-159 (2004).
71. + (GIRK) channels composed of GIRK2 and GIRK3. J. Biol. Chem. 275 (46), 36211-36216 (2000).
72. KACh in atrial fibrillation using a mouse knockout model. J. Am. Coll. Cardiol. 37 (8), 2136-2143 (2001).
73. Lloyd-Jones DM, Wang TJ, Leip EP et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 110 (9), 1042-1046 (2004).
74. KACh. J. Biol. Chem. 277 (50), 48282-48288 (2002).
75. Wickman K, Nemec J, Gendler SJ, Clapham DE. Abnormal heart rate regulation in GIRK4 knockout mice. Neuron 20 (1), 103-114 (1998).
76. Ehrlich JR, Nattel S. Novel approaches for pharmacological management of atrial fibrillation. Drugs 69 (7), 757-774 (2009).
77. Kaneko N, Matsuda R, Hata Y, Shimamoto K. Pharmacological characteristics and clinical applications of K201. Curr. Clin. Pharmacol. 4 (2), 126-131 (2009).
78. Watanabe Y, Hara Y, Tamagawa M, Nakaya H. Inhibitory effect of amiodarone on the muscarinic acetylcholine receptor-operated potassium current in guinea pig atrial cells. J. Pharmacol. Exp. Ther. 279 (2), 617-624 (1996).
79. Gogelein H, Brendel J, Steinmeyer K et al. Effects of the atrial antiarrhythmic drug AVE0118 on cardiac ion channels. Naunyn Schmiedebergs Arch. Pharmacol. 370 (3), 183-192 (2004).
80. Matsuda T, Ito M, Ishimaru S et al. Blockade by NIP-142, an antiarrhythmic agent, of carbachol-induced atrial action potential shortening and GIRK1/4 channel. J. Pharmacol. Sci. 101 (4), 303-310 (2006).
81. KACh blocker, NIP-151: a comparison with an IKr-blocker dofetilide. J. Cardiovasc. Pharmacol. 51 (2), 162-169 (2008).
82. B receptors to control rhythmic hippocampal activity. Neuron 25 (3), 673-681 (2000).
83. Lujan R, Maylie J, Adelman JP. New sites of action for GIRK and SK channels. Nat. Rev. Neurosci. 10 (7), 475-480 (2009).
84. Pravetoni M, Wickman K. Behavioral characterization of mice lacking GIRK/Kir3 channel subunits. Genes Brain Behav. 7 (5), 523-531 (2008).
85. Marker CL, Cintora SC, Roman MI, Stoffel M, Wickman K. Hyperalgesia and blunted morphine analgesia in G protein-gated potassium channel subunit knockout mice. Neuroreport 13 (18), 2509-2513 (2002).
86. + channels formed by GIRK1 and GIRK2 subunits modulate thermal nociception and contribute to morphine analgesia. J. Neurosci. 24 (11), 2806-2812 (2004).
87. Morgan AD, Carroll ME, Loth AK, Stoffel M, Wickman K. Decreased cocaine self-administration in Kir3 potassium channel subunit knockout mice. Neuropsychopharmacol. 28 (5), 932-938 (2003).
88. + channels by various antidepressant drugs. Neuropsychopharmacol. 29 (10), 1841-1851 (2004).
89. + (GIRK) channels expressed in Xenopus oocytes. Br. J. Pharmacol. 129 (8), 1716-1722 (2000).
90. + channels by fluoxetine (Prozac). Br. J. Pharmacol. 138 (6), 1119-1128 (2003).
91. + channels. Proc. Natl Acad. Sci. USA 98 (11), 6482-6487 (2001).
92. + channels. Neuropharmacol. 56 (2), 499-506 (2009).
93. Weigl LG, Schreibmayer W. G protein-gated inwardly rectifying potassium channels are targets for volatile anesthetics. Mol. Pharmacol. 60 (2), 282-289 (2001).
94. Kuzhikandathil EV, Oxford GS. Classic D1 dopamine receptor antagonist R- (+) -7-chloro-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzaze pine hydrochloride (SCH23390) directly inhibits G proteincoupled inwardly rectifying potassium channels. Mol. Pharmacol. 62 (1), 119-126 (2002).
95. Ulens C, Daenens P, Tytgat J. The dual modulation of GIRK1/GIRK2 channels by opioid receptor ligands. Eur. J. Pharmacol. 385 (2-3), 239-245 (1999).
96. Pan HL, Wu ZZ, Zhou HY, Chen SR, Zhang HM, Li DP. Modulation of pain transmission by G-protein-coupled receptors. Pharmacol. Ther. 117 (1), 141-161 (2008).
97. Ueda H, Ueda M. Mechanisms underlying morphine analgesic tolerance and dependence. Front. Biosci. 14, 5260-5272 (2009).
98. Li L, Head V, Timpe LC. Identification of an inward rectifier potassium channel gene expressed in mouse cortical astrocytes. Glia 33 (1), 57-71 (2001).
99. Kofuji P, Biedermann B, Siddharthan V et al. Kir potassium channel subunit expression in retinal glial cells. implications for spatial potassium buffering. Glia 39 (3), 292-303 (2002).
100. Lang F, Vallon V, Knipper M, Wangemann P. Functional significance of channels and transporters expressed in the inner ear and kidney. Am. J. Physiol. Cell. Physiol. 293 (4), C1187-C1208 (2007).
101. + channel at the basolateral membrane of the mouse distal convoluted tubule. similarities with Kir4-Kir5.1 heteromeric channels. J. Physiol. 538 (Pt 2), 391-404 (2002).
102. + channel in the basolateral membrane of mouse renal collecting duct principal cells. Am. J. Physiol. Renal Physiol. 294 (6), F1398-F1407 (2008).
103. + channels. EMBO. J. 15 (12), 2980-2987 (1996).
104. Kofuji P, Ceelen P, Zahs KR, Surbeck LW, Lester HA, Newman EA. Genetic inactivation of an inwardly rectifying potassium channel (Kir4.1 subunit) in mice: phenotypic impact in retina. J. Neurosci. 20 (15), 5733-5740 (2000).
105. Neusch C, Rozengurt N, Jacobs RE, Lester HA, Kofuji P. Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. J. Neurosci. 21 (15), 5429-5438 (2001).
106. Rozengurt N, Lopez I, Chiu CS, Kofuji P, Lester HA, Neusch C. Time course of inner ear degeneration and deafness in mice lacking the Kir4.1 potassium channel subunit. Hear. Res. 177 (1-2), 71-80 (2003).
107. Bockenhauer D, Feather S, Stanescu HC et al. Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N. Engl. J. Med. 360 (19), 1960-1970 (2009).
108. Scholl UI, Choi M, Liu T et al. Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10. Proc. Natl Acad. Sci. USA 106 (14), 5842-5847 (2009).
109. Butt AM, Kalsi A. Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions. J. Cell. Mol. Med. 10 (1), 33-44 (2006).
110. Su S, Ohno Y, Lossin C, Hibino H, Inanobe A, Kurachi Y. Inhibition of astroglial inwardly rectifying Kir4.1 channels by a tricyclic antidepressant, nortriptyline. J. Pharmacol. Exp. Ther. 320 (2), 573-580 (2007).
111. Ohno Y, Hibino H, Lossin C, Inanobe A, Kurachi Y. Inhibition of astroglial Kir4.1 channels by selective serotonin reuptake inhibitors. Brain Res. 1178, 44-51 (2007).
112. ATP channel therapeutics at the bedside. J. Mol. Cell. Cardiol. 39 (1), 99-112 (2005).
113. ATP channel pharmacogenomics: from bench to bedside. Clin. Pharmacol. Ther. 83 (2), 354-357 (2008).
114. Lefer DJ, Nichols CG, Coetzee WA. Sulfonylurea receptor 1 subunits of ATP-sensitive potassium channels and myocardial ischemia/reperfusion injury. Trends Cardiovasc. Med. 19 (2), 61-67 (2009).
115. Hejtmancik JF, Jiao X, Li A et al. Mutations in KCNJ13 cause autosomal-dominant snowflake vitreoretinal degeneration. Am. J. Hum. Genet. 82 (1), 174-180 (2008).
116. + channel in guinea pig distal colonic crypts. Am. J. Physiol. Cell. Physiol. 282 (4), C719-C735 (2002).