Development of a QPatch automated electrophysiology assay for identifying KCa3.1 inhibitors and activators

Assay and Drug Development Technologies

Volumn 11, Issue 9-10, 2013, Pages 551-560

  Jenkins, David Paul ^a   Yu, Weifeng ^b   Brown, Brandon M ^a   Løjkner, Lars Damgaard ^b   Wulff, Heike ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Sophion Bioscience Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM ACTIVATED POTASSIUM CHANNEL; CALCIUM ACTIVATED POTASSIUM CHANNEL KCA3.1; CALCIUM ACTIVATED POTASSIUM CHANNEL KCA3.1 ACTIVATOR; CALCIUM ACTIVATED POTASSIUM CHANNEL KCA3.1 INHIBITOR; CALCIUM ION; POTASSIUM CHANNEL BLOCKING AGENT; POTASSIUM CHANNEL STIMULATING AGENT; UNCLASSIFIED DRUG;

ARTICLE; CALCIUM CELL LEVEL; CHANNEL GATING; CONTROLLED STUDY; DRUG DETERMINATION; DRUG POTENCY; DRUG SCREENING; HUMAN; HUMAN CELL; PATCH CLAMP TECHNIQUE; QPATCH BASED ELECTROPHYSIOLOGY ASSAY;

BIOLOGICAL ASSAY; DRUG EVALUATION, PRECLINICAL; FLOW CYTOMETRY; FLOW INJECTION ANALYSIS; HEK293 CELLS; HUMANS; INTERMEDIATE-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS; ION CHANNEL GATING; MEMBRANE POTENTIALS; PATCH-CLAMP TECHNIQUES; POTASSIUM CHANNEL BLOCKERS; ROBOTICS;

EID: 84890903984     PISSN: 1540658X     EISSN: 15578127     Source Type: Journal    
DOI: 10.1089/adt.2013.543     Document Type: Article

References (57)

1. Joiner WJ, Wang LY, Tang MD, Kaczmarek LK: hSK4, a member of a novel subfamily of calcium-activated potassium channels. Proc Natl Acad Sci USA 1997;94:11013-11018.
2. Logsdon NJ, Kang J, Togo JA, Christian EP, Aiyar J: A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes. J Biol Chem 1997;272:32723-32726.
3. Vandorpe DH, Shmukler BE, Jiang L, et al.: cDNA cloning and functional characterization of the mouse Ca2 + -gated K+ channel, mIK1. Roles in regulatory volume decrease and erythroid differentiation. J Biol Chem 1998; 273:21542-21553.
4. Pena TL, Rane SG: The fibroblast intermediate-conductance KCa channel, FIK, as a prototype for the cell growth regulatory function of the IK channel family. J Membr Biol 1999;172:249-257.
5. Kohler R, Wulff H, Eichler I, et al.: Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis. Circulation 2003;108:1119-1125.
6. Heitzmann D, Warth R: Physiology and pathophysiology of potassium channels in gastrointestinal epithelia. Physiol Rev 2008;88:1119-1182.
7. Xia XM, Fakler B, Rivard A, et al.: Mechanism of calcium gating in smallconductance calcium-activated potassium channels. Nature 1998;395:503-507.
8. Fanger CM, Ghanshani S, Logsdon NJ, et al.: Calmodulin mediates calciumdependent activation of the intermediate conductance KCa channel, IKCa1. J Biol Chem 1999;274:5746-5754.
9. Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H: International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels. Pharmacol Rev 2005;57:463-472.
10. Cahalan MD, Chandy KG: The functional network of ion channels in T lymphocytes. Immunol Rev 2009;231:59-87.
11. Wulff H, Castle NA: Therapeutic potential of KCa3.1 blockers: recent advances and promissing trends. Expert Rev Clin Pharmacol 2010;3:385-396.
12. Ghanshani S, Wulff H, Miller MJ, et al.: Up-regulation of the IKCa1 potassium channel during T-cell activation: molecular mechanism and functional consequences. J Biol Chem 2000;275:37137-37149.
13. Di L, Srivastava S, Zhdanova O, et al.: Inhibition of the K+ channel KCa3.1 ameliorates T cell-mediated colitis. Proc Natl Acad Sci USA 2010;107:1541-1546.
14. Wulff H, Knaus HG, Pennington M, Chandy KG: K + channel expression during B-cell differentiation: implications for immunomodulation and autoimmunity. J Immunol 2004;173:776-786.
15. Reich EP, Cui L, Yang L, et al.: Blocking ion channel KCNN4 alleviates the symptoms of experimental autoimmune encephalomyelitis in mice. Eur J Immunol 2005;35:1027-1036.
16. Grgic I, Kiss E, Kaistha BP, et al. Renal fibrosis is attenuated by targeted disruption of KCa3.1 potassium channels. Proc Natl Acad Sci USA 2009;106: 14518-14523.
17. Girodet PO, Ozier A, Carvalho G, et al.: Ca2 + -activated K + channel-3.1 blocker TRAM-34 attenuates airway remodeling and eosinophilia in a murine asthma model. Am J Respir Cell Mol Biol 2013;48:212-219.
18. Van Der Velden J, Sum G, Barker D, et al.: KCa3.1 channel-blockade attenuates airway pathophysiology in a sheep model of chronic aAsthma. PLoS One 2013;8:e66886.
19. Brugnara C: Sickle cell disease: from membrane pathophysiology to novel therapies for prevention of erythrocyte dehydration. J Pediatr Hematol Oncol 2003;25:927-933.
20. Brugnara C, Gee B, Armsby CC, et al.: Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease. J Clin Invest 1996;97:1227-1234.
21. Rufo PA, Merlin D, Riegler M, et al.: The antifungal antibiotic, clotrimazole, inhibits chloride secretion by human intestinal T84 cells via blockade of distinct basolateral K + conductances. Demonstration of efficacy in intact rabbit colon and in an in vivo mouse model of cholera. J Clin Invest 1997;100:3111-3120.
22. Edwards G, Feletou M, Weston AH: Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflugers Arch 2010;459:863-879.
23. Grgic I, Kaistha BP, Hoyer J, Kohler R: Endothelial Ca + -activated K+ channels in normal and impaired EDHF-dilator responses - relevance to cardiovascular pathologies and drug discovery. Br J Pharmacol 2009;157:509-526.
24. Kohler R, Kaistha BP, Wulff H: Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease. Expert Opin Ther Targets 2010;14: 143-155.
25. Dalsgaard T, Kroigaard C, Simonsen U: Calcium-activated potassium channels - a therapeutic target for modulating nitric oxide in cardiovascular disease? Expert Opin Ther Targets 2010;14:825-837.
26. Brahler S, Kaistha A, Schmidt VJ, et al.: Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension. Circulation 2009;119:2323-2332.
27. Sankaranarayanan A, Raman G, Busch C, et al.: Naphtho[1,2-d]thiazol-2- ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure. Mol Pharmacol 2009;7:281-295.
28. Damkjaer M, Nielsen G, Bodendiek S, et al.: Pharmacological activation of KCa3.1/KCa2.3 channels produces endothelial hyperpolarization and lowers blood pressure in conscious dogs. Br J Pharmacol 2012;165:223-234.
29. Radtke J, Schmidt K, Wulff H, Kohler R, de Wit C: Activation of K 3.1 by SKA-31 induces arteriolar dilation and lowers blood pressure in normo- and hypertensive connexin40-deficient mice. Br J Pharmacol 2013;170:293-303.
30. Wulff H, Kolski-Andreaco A, Sankaranarayanan A, Sabatier JM, Shakkottai V: Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications. Cur Med Chem 2007;14: 1437-1457.
31. Chen YJ, Raman G, Bodendiek S, O'Donnell ME, Wulff H: The KCa3.1 blocker TRAM-34 reduces infarction and neurological deficit in a rat model of ischemia/ reperfusion stroke. J Cereb Blood Flow Metab 2011;31:2363-2374.
32. Maezawa I, Jenkins DP, Jin BE, Wulff H: Microglial KCa3.1 channels as a potential therapeutic target for Alzheimer's disease. Inter J Alzheimer's Dis 2012;2012:868972.
33. Maezawa I, Zimin P, Wulff H, Jin LW: A-beta oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity. J Biol Chem 2011;286:3693-3706.
34. Jorgensen S, Dyhring T, Brown DT, Strobaek D, Christophersen P, Demnitz J: A high-throughput screening campaign for detection of Ca2 + -activated K+ channel activators and inhibitors using a fluorometric imaging plate readerbased Tl + -influx assay. Assay Drug Dev Technol 2013;11:163-172.
35. Wulff H, Miller MJ, Haensel W, Grissmer S, Cahalan MD, Chandy KG: Design of a potent and selective inhibitor of the intermediate-conductance Ca2 + -activated K+ channel, IKCa1: A potential immunosuppressant. Proc Natl Acad Sci USA 2000;97:8151-8156.
36. Strøbæk D, Brown DT, Jenkins DP, et al.: NS6180, a new KCa3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease. Br J Pharmacol 2013;168:432-444.
37. Patton C: WebMaxC Standard. Online, 2009 Jul 3. Available at: http:// maxchelator.stanford.edu/webmaxc/webmaxcS.htm (accessed April 2013).
38. Li W, Halling DB, Hall AW, Aldrich RW: EF hands at the N-lobe of calmodulin are required for both SK channel gating and stable SK-calmodulin interaction. J Gen Physiol 2009;134:281-293.
39. Wulff H, Gutman GA, Cahalan MD, Chandy KG: Delination of the clotrimazole/ TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel IKCa1. J Biol Chem 2001;276:32040-32045.
40. Stocker JW, De Franceschi L, McNaughton-Smith GA, Corrocher R, Beuzard Y, Brugnara C: ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice. Blood 2003;101:2412-2418.
41. Ataga KI, Reid M, Ballas SK, et al.: Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: a phase III randomized, placebo-controlled, double-blind study of the Gardos channel blocker senicapoc (ICA-17043). Br J Haematol 2011;153:92-104.
42. Korsgaard MP, Strøbæk D, Christophersen P: Automated planar electrode electrophysiology in drug discovery: examples of the use of QPatch in basic characterization and high content screening on Na(v), K(Ca)2.3, and K(v)11.1 channels. Comb Chem High Throughput Screen 2009;12:51-63.
43. Terstappen GC: Functional analysis of native and recombinant ion channels using a high-capacity nonradioactive rubidium efflux assay. Anal Biochem 1999;2722:149-155.
44. Hougaard C, Eriksen BL, Jorgensen S, et al.: Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2 + -activated K + channels. Br J Pharmacol 2007;151:655-665.
45. Jorgensen S, Johansen TH, Dyhring T: Fluorescence-based Tl + -influx assays as a novel approach for characterization of small-conductance Ca2 + -activated K + channel modulators. Methods Mol Biol 2008;491:257-266.
46. John VH, Dale TJ, Hollands EC, et al.: Novel 384-well population patch clamp electrophysiology assays for Ca2 + -activated K + channels. J Biomol Screen 2007;12:50-60.
47. Ayabe T, Wulff H, Darmoul D, Cahalan MD, Chandy KG, Ouellette AJ: Modulation of mouse paneth cell alpha-defensin secretion by mIKCa1, a Ca2 + -activated, intermediate-conductance otassium channel. J Biol Chem 2002;277:3793-3800.
48. Beeton C, Wulff H, Barbaria J, et al.: Selective blockade of T lymphocyte K + channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Proc Natl Acad Sci USA 2001;98:13942-13947.
49. Hougaard C, Jensen ML, Dale TJ, et al.: Selective activation of the SK1 subtype of human small-conductance Ca2 + -activated K+ channels by 4-(2-methoxyphenylcarbamoyloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester (GW542573) is dependent on serine 293 in the S5 segment. Mol Pharmacol 2009;76:569-578.
50. Pedersen KA, Schroder RL, Skaaning-Jensen B, Strøbæk D, Olesen SP, Christophersen P: Activation of the human intermediate-conductance Ca2 + - activated K+ channel by 1-ethyl-2-benzimidazolinone is strongly Ca2 + - dependent. Biochim Biophys Acta 1999;1420:231-240.
51. Pedarzani P, Mosbacher J, Rivard A, et al. Control of electrical activity in central neurons by modulating the gating of small conductance Ca2 + -activated K + channels. J Biol Chem 2001;276:9762-9769.
52. Hougaard C, Hammami S, Eriksen BL, et al.: Evidence for a common pharmacological interaction site on K(Ca)2 channels providing both selective activation and selective inhibition of the human K(Ca)2.1 subtype. Mol Pharmacol 2012;81:210-209.
53. Gerlach AC, Syme CA, Giltinan L, Adelman JP, Devors DC: ATP-dependent activation of the intermediate conductance, Ca2 + -activated K+ channel, hIK1, is conferred by a C-terminal domain. J Biol Chem 2001;276:10963-10970.
54. Jones HM, Bailey MA, Baty CJ, et al.: An NH2-terminal multi-basic RKR motif is required for the ATP-dependent regulation of hIK1. Channels (Austin) 2007;1:80-91.
55. Gerlach AC, Gangopadhyay NN, Devor DC: Kinase-dependent regulation of the intermediate conductance, calcium-dependent potassium channel, hIK1. J Biol Chem 2000;275:585-598.
56. Srivastava S, Li Z, Ko K, et al.: Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells. Mol Cell 2006;24:665-675.
57. Srivastava S, Zhdanova O, Di L, et al.: Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K + channel KCa3.1. Proc Natl Acad Sci USA 2008;105:14442-14446.