Potassium ion channels and human disease: Phenotypes to drug targets?

Current Opinion in Biotechnology

Volumn 9, Issue 6, 1998, Pages 565-572

  Curran, Mark E ^a  

^a Axys Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ION CHANNEL; POTASSIUM CHANNEL;

CHROMOSOME MUTATION; DRUG DETERMINATION; DRUG INDUSTRY; DRUG SCREENING; DRUG TARGETING; HUMAN; INHERITANCE; MOLECULAR WEIGHT; MULTIGENE FAMILY; PHARMACOGENETICS; PHENOTYPE; PRIORITY JOURNAL; REVIEW;

EID: 0032402903     PISSN: 09581669     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0958-1669(98)80133-X     Document Type: Article

References (97)

1. Hille B. edn 2 Ionic Channels of Excitable Membranes. 1992;Sinauer, Sunderland, MA.
2. + channel structure, function and physiological importance.
3. Papazian DM, Schwarz TL, Tempel BL, Jan YN, Jan LY. Cloning of genomic and complementary DNA from Shaker, a putative potassium channel gene from Drosophila. Science. 237:1987;749-753.
4. Tempel BL, Papazian DM, Schwarz TL, Jan YN, Jan LY. Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila. Science. 237:1987;770-775.
5. Iverson LE, Tanouye MA, Lester HA, Davidson N, Rudy B. A-type potassium channels expressed from Shaker locus cDNA. Proc Natl Acad Sci USA. 85:1988;5723-5727.
6. Pongs O, Kecskemethy N, Muller R, Krah-Jentgens I, Baumann A, Kiltz HH, Canal I, Llamazares S, Ferrus A. Shaker encodes a family of putative potassium channel proteins in the nervous system of Drosophila. EMBO J. 7:1988;1087-1096.
7. Ganetzky B, Warmke JW, Robertson G, Pallanck L. New potassium gene families in flies and mammals: from mutants to molecules. Dawson DC, Frizzell RA. Ion Channels and Genetic Diseases. 1995;29-39 Rockefeller University Press, New York.
8. MacKinnon R. Determination of the subunit stoichiometry of a voltage-activated potassium channel. Nature. 350:1991;232-235.
9. Yang J, Jan YN, Jan LY. Determination of the subunit stoichiometry of an inwardly rectifying potassium channel. Neuron. 15:1995;1441-1447.
10. Kreusch A, Pfaffinger PJ, Stevens CF, Choe S. Crystal structure of the tetramerization domain of the Shaker potassium channel. of outstanding interest Nature. 392:1998;945-948 See annotation to [11].
11. + channels and co-crystal structures with attached βs and channel-active compounds with great interest.
12. + channel subtypes.
13. Ketchum KA, Joiner WJ, Sellers AJ, Kaczmarek LK, Goldstein SA. A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Nature. 376:1995;690-695.
14. Goldstein SA, Price LA, Rosenthal DN, Pausch MH. ORK1, a potassium-selective leak channel with two pore domains cloned from Drosophila melanogaster by expression in Saccharomyces cerevisiae. Proc Natl Acad Sci USA. 93:1996;13256-13261.
15. + channel with a novel structure. EMBO J. 15:1996;1004-1011.
16. + channel to sense external pH variations near physiological pH. EMBO J. 16:1997;5464-5471.
17. + channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO J. 17:1998;3297-3308.
18. Leonoudakis D, Gray AT, Winegar BD, Kindler CH, Harada M, Taylor DM, Chavez RA, Forsayeth JR, Yost CS. An open rectifier potassium channel with two pore domains in tandem cloned from rat cerebellum. J Neurosci. 18:1998;868-877.
19. Xu J, Yu W, Wright JM, Raab RW, Li M. Distinct functional stoichiometry of potassium channel beta subunits. Proc Natl Acad Sci USA. 95:1998;1846-1851.
20. Xu J, Li M. Auxiliary subunits of Shaker-type potassium channels. Trends Cardiol Med. 8:1998;229-234.
21. Kaczmarek LK, Blumenthal EM. Properties and regulation of the minK potassium channel protein. Physiol Rev. 3:1997;627-641.
22. Chouinard SW, Wilson GF, Schlimgen AK, Ganetzky B. A potassium channel beta subunit related to the aldo-keto reductase superfamily is encoded by the Drosophila hyperkinetic locus. Proc Natl Acad Sci USA. 92:1995;6763-6767.
23. + channels. Neuron. 16:1996;1011-1017.
24. + channel regulatory protein, KChAP. of special interest J Biol Chem. 273:1998;11745-11751 Understanding the role of regulatory proteins in enhancing and modifying channel activities is critical to evaluating channels as therapeutic targets. This paper describes characterization of a novel channel modifier, KChAP. Identified by yeast two-hybrid approaches, KChAP appears to increase expression levels of certain channels. Although the function of KChAP is not yet clear, the authors have speculated that KChAP may function as a channel-specific chaperone protein.
25. Bulman DE. Phenotype variation and newcomers in ion channel disorders. Hum Mol Genet. 6:1997;1679-1685.
26. Ackerman MJ, Clapham DE. Ion channels: basic science and clinical disease. N Engl J Med. 336:1997;1575-1586.
27. Goldstein SA, Colatsky TJ. Ion channels: too complex for rational drug design? Neuron. 16:1996;913-919.
28. Grissmer S. Potassium channels still hot. Trends Pharmacol Sci. 18:1997;347-350.
29. Sanguinetti MC, Spector PS. Potassium channelopathies. Neuropharmacol. 36:1997;755-762.
30. Sanguinetti MC. Potassium channels of cardiac myocytes. Methods Neurosci. 19:1994;205-219.
31. Kass RC, Freeman LC. Potassium channels in the heart. Cellular, molecular and clinical implications. Trends Cardiovasc Med. 3:1993;149-159.
32. Deal KK, England SK, Tamkun MM. Molecular physiology of cardiac potassium channels. Physiol Rev. 76:1996;49-67.
33. + current: differential sensitivity to block by Class III antiarrhythmic agents. J Gen Physiol. 96:1990;195-215.
34. + channels. Heart Vessels. 12:1997;170-172.
35. Keating MT, Sanguinetti MC. Molecular genetic insights into cardiovascular disease. Science. 272:1996;681-685.
36. Warmke JW, Ganetzky B. A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci USA. 91:1994;3438-3442.
37. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause Long QT syndrome. Cell. 80:1995;795-804.
38. Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERB encodes the IKr potassium channel. Cell. 81:1995;299-307.
39. + channels expressed in Xenopus oocytes. Am J Physiol. 272:1997;1309-1314.
40. Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, Shen J, Timothy KW, Vincent GM, deJager T, et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 12:1996;17-23.
41. Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MT. Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks)potassium channel. Nature. 384:1996;80-83.
42. Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G. K(V)LQT1 and IsK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature. 384:1996;78-80.
43. Splawski I, Tristani-Firouzi M, Lehmann MH, Sanguinetti MC, Keating MT. Mutations in the hminK gene cause long QT syndrome and suppress Iks function. Nat Genet. 17:1997;338-340.
44. Zipes DP. Proarrhythmic effects of antiarrhythmic drugs. Am J Cardiol. 59:1987;26-31.
45. Roden DM. Arrhythmogenic potential of class III antiarrhythmic agents: comparison with class I agents. Singh BN, Kisco MT. Control of Cardiac Arrhythmias by Lengthening Repolarization. 1988;559-576 Futura Publishing Co, New York.
46. Compton SJ, Lux RL, Ramsey MR, Strelich KR, Sanguinetti MC, Green LS, Keating MT, Mason JW. Genetically defined therapy of inherited long-QT syndrome. Correction of abnormal repolarization by potassium. Circulation. 94:1996;1018-1022.
47. + channel opener in the LQT1 form of congenital long-QT syndrome. Circulation. 97:1998;1581-1588.
48. + channel cDNAs from human ventricle. FASEB J. 5:1991;331-337.
49. Curran ME, Landes GM, Keating MT. Molecular cloning, characterization, and genomic localization of a human potassium channel gene. Genomics. 12:1992;729-737.
50. + current in cultured adult human atrial myocytes. Circ Res. 80:1997;572-579.
51. + current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ Res. 80:1997;772-781.
52. Prystowsky EN, Katz A. Atrial fibrillation. Topal EJ. Comprehensive Cardiovascular Medicine. 1998;1827-1859 Lippincott-Raven Publishers, Philadelphia.
53. Ellenbogen KA, Clemo HF, Stambler BS, Wood MA, VanderLugt JT. Efficacy of ibutilide for termination of atrial fibrillation and flutter. Am J Cardiol. 78:1996;42-45.
54. Doupnik CA, Davidson N, Lester HA. The inward rectifier potassium channel family. Curr Opin Neurobiol. 5:1995;268-277.
55. Isomoto S, Kondo C, Kurachi Y. Inwardly rectifying potassium channels: their molecular heterogeneity and function. Jpn J Physiol. 47:1997;11-39.
56. Brown AM. Membrane-delimited cell signaling complexes: direct ion channel regulation by G proteins. J Membr Biol. 131:1993;93-104.
57. + channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins. Nature. 374:1995;135-141.
58. + channel, IKACh. J Biol Chem. 273:1998;5271-5278.
59. Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, Tibbs GR. Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain. of outstanding interest Cell. 93:1998;717-729 This manuscript describes the biophysical characterization of mBCNG-1 and demonstrates that this channel is indistinguishable from the pacemaker channel in brain and similar to pacemaker currents in cardiac cells. The authors speculate on the role of these channels in human disease and suggest that they will be relevant to rhythm disorders affecting brain and heart tissues.
60. Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M. A family of hyperpolarization-activated mammalian cation channels. of outstanding interest Nature. 393:1998;587-591 Published simultaneously with the paper by Santoro [59], the authors report biophysical characterization of a single hyperpolarization channel and molecular identification of two highly related genes.
61. Gauss R, Seifert R, Kaupp UB. Molecular identification of a hyperpolarization-activated channel in sea urchin sperm. Nature. 393:1998;583-587.
62. Giebisch GH. Renal potassium transport: mechanisms and regulation. Am J Physiol. 274:1998;817-833.
63. Ho K, Nichols CG, Lederer WJ, Lytton J, Vassilev PM, Kanazirska MV, Hebert SC. Cloning and expression of an inwardly rectifying ATP-regulated potassium channel. Nature. 362:1993;31-38.
64. Shuck ME, Bock JH, Benjamin CW, Tsai TD, Lee KS, Slightom JL, Bienkowski MJ. Cloning and characterization of multiple forms of the human kidney ROM-K potassium channel. J Biol Chem. 269:1994;24261-24270.
65. Mutations in the gene encoding the inwardly-rectifying renal potassium channel, ROMK, cause the antenatal variant to Bartter syndrome: evidence for genetic heterogeneity. Hum Mol Genet. 6:1997;17-26.
66. + channel ROMK. Nat Genet. 14:1996;152-156.
67. + channel function. Biochem Biophys Res Commun. 230:1997;641-645.
68. + channels in pancreatic cardiac, and vascular smooth muscle cells. Am J Physiol. 274:1998;25-37.
69. Shyng S, Nichols CG. Octameric stoichiometry of the KATP channel complex. J Gen Physiol. 110:1997;655-664.
70. + channel. FEBS Lett. 409:1997;232-236.
71. Nestorowicz A, Inagaki N, Gonoi T, Schoor KP, Wilson BA, Glaser B, Landau H, Stanley CA, Thornton PS, Seino S, Permutt MA. A nonsense mutation in the inward rectifier potassium channel gene, Klr6.2, is associated with familial hyperinsulinism. Diabetes. 46:1997;1743-1748.
72. Thomas P, Ye Y, Lightner E. Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy. Hum Mol Genet. 5:1996;1809-1812.
73. Miki T, Tashiro F, Iwanaga T, Nagashima K, Yoshitomi H, Aihara H, Nitta Y, Gonoi T, Inagaki N, Miyazaki JI, Seino S. Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel. Proc Natl Acad Sci USA. 94:1997;11969-11973.
74. + channels in pulmonary arterial smooth muscle cells. Am J Physiol. 274:1998;L621-L635.
75. Kozlowski RZ. Ion channels, oxygen sensation and signal transduction in pulmonary arterial smooth muscle. Cardiovasc Res. 30:1995;318-325.
76. + current that is active at resting potential in rabbit pulmonary artery smooth muscle cells. J Physiol (Lond). 496:1996;407-420.
77. 2-sensing potassium current. Br J Pharmacol. 120:1997;1461-1470.
78. + channel in oxygen-sensitive pulmonary artery myocytes. EMBO J. 16:1997;6615-6625.
79. Gardos G. Studies on potassium permeability changes in human erythrocytes. Experientia. 23:1967;19-20.
80. Brugnara C. Erythrocyte membrane transport physiology. Curr Opin Hematol. 4:1997;122-127.
81. + channel in red blood cells. The molecular characterization of hIK1 should facilitate identification of improved therapeutics for treating sickle cell anemia.
82. + channel, mIK1. Roles in regulatory volume decrease and erythroid differentiation. J Biol Chem. 273:1998;21542-21553.
83. Brugnara C, Gee B, Armsby CC, Kurth S, Sakamoto M, Rifai N, Alper SL, Platt OS. Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell diseases. J Clin Invest. 97:1996;1227-1234.
84. Meisler MH, Sprunger LK, Plummer NW, Escayg A, Jones JM. Ion channel mutations in mouse models of inherited neurological disease. Ann Med. 29:1997;569-574.
85. Leppert M, McMahon WM, Quattlebaum TG, Bjerre I, Zonana J, Shevell MI, Andermann E, Rosales TO, Ronen GM, Connolly M. Searching for human epilepsy genes: a progress report. Brain Pathol. 3:1993;357-369.
86. + currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice. Proc Natl Acad Sci USA. 94:1997;12210-12217.
87. Patil N, Cox DR, Bhat D, Faham M, Myers RM, Peterson AS. A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation. Nat Genet. 11:1995;126-129.
88. + channel GIRK2. Proc Natl Acad Sci USA. 94:1997;923-927.
89. + channels. Science. 272:1996;1950-1953.
90. + channels. Neuron. 16:1996;321-331.
91. Plouin P. Benign familial neonatal convulsions. Malafosse A. Idiopathic Generalized Epilepsies: Clinical, Experimental and Genetic Aspects. 1994;39-44 John Libbey, London.
92. Charlier C, Singh NA, Ryan SG, Lewis TB, Reus BE, Leach RJ, Leppert M. A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. of special interest Nat Genet. 18:1998;53-55 See annotation to [94].
93. Singh NA, Charlier C, Stauffer D, DuPont BR, Leach RJ, Melis R, Ronen GM, Bjerre I, Quattlebaum T, Murphy JV. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. of special interest Nat Genet. 18:1998;25-29 See annotation to [94].
94. Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ, Steinlein OK. A potassium channel mutation in neonatal human epilepsy. of special interest Science. 279:1998;403-406 This paper and those by Charlier [92] and Singh [93] illustrate how molecular genetics and genomics approaches reveal genes of therapeutic relevance. This is the culmination of almost a decade of effort by the Leppert group and others to clone epilepsy genes. The identification of KCNQ2 and KCNQ3 provides new insight into these conditions and suggests immediate targets for these disorders.
95. Yang WP, Levesque PC, Little WA, Conder ML, Ramakrishnan P, Neubauer MG, Blanar MA. Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy. J Biol Chem. 273:1998;19419-19423.
96. Cahalan MD, Chandy KG. Ion channels in the immune system as targets for immunosuppression. Curr Opin Biotechnol. 8:1997;749-756.
97. + current highly conserved in tumors of different histogenesis: a selective advantage for cancer cells? Cancer Res. 58:1998;815-822.