A Novel High-Throughput Screening Assay for HCN Channel Blocker Using Membrane Potential-Sensitive Dye and FLIPR

Journal of Biomolecular Screening

Volumn 14, Issue 9, 2009, Pages 1119-1128

  Vasilyev, Dmitry V ^a   Shan, Qin J ^a   Lee, Yan T ^a   Soloveva, Veronica ^a   Nawoschik, Stanley P ^a   Kaftan, Edward J ^a   Dunlop, John ^a   Mayer, Scott C ^a   Bowlby, Mark R ^a  

^a PFIZER INC   (United States)

Author keywords

FLIPR; HCN1 channel; high throughput screening; Ion Works; membrane potential sensitive dye

Indexed keywords

CYCLIC NUCLEOTIDE GATED CHANNEL; FLUORESCENT DYE; HYPERPOLARIZATION ACTIVATED CATION CHANNEL; HYPERPOLARIZATION-ACTIVATED CATION CHANNEL; POTASSIUM CHANNEL;

ANIMAL; ARTICLE; BIOASSAY; CELL LINE; CELL MEMBRANE POTENTIAL; CHEMISTRY; DRUG ANTAGONISM; DRUG DESIGN; ELECTROPHYSIOLOGY; EVALUATION; HIGH THROUGHPUT SCREENING; HUMAN; INSTRUMENTATION; METABOLISM; METHODOLOGY; PHYSIOLOGY;

ANIMALS; BIOLOGICAL ASSAY; CELL LINE; CYCLIC NUCLEOTIDE-GATED CATION CHANNELS; DRUG DESIGN; ELECTROPHYSIOLOGY; FLUORESCENT DYES; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MEMBRANE POTENTIALS; POTASSIUM CHANNELS;

EID: 74049095173     PISSN: 10870571     EISSN: None     Source Type: Journal    
DOI: 10.1177/1087057109345526     Document Type: Article

References (30)

1. Mathes C.: Ion channels in drug discovery and development. Drug Discov Today 2003; 8: 1022-1024.
2. Robinson RB, Siegelbaum SA: Hyperpolarization-activated cation currents: from molecules to physiological function. Annu Rev Physiol 2003; 65: 453-480.
3. Diaz A., Tardif JC: Heart rate slowing versus other pharmacological antianginal strategies. Adv Cardiol 2006; 43: 65-78.
4. Chaplan SR, Guo HQ, Lee DH, Luo L., Liu C., Kuei C., et al: Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain. J Neurosci 2003; 23: 1169-1178.
5. Dalle C., Eisenach JC: Peripheral block of the hyperpolarization-activated cation current (Ih) reduces mechanical allodynia in animal models of postoperative and neuropathic pain. Reg Anesth Pain Med 2005; 30: 243-248.
6. Vasilyev DV, Barish ME: Postnatal development of the hyperpolarization-activated excitatory current Ih in mouse hippocampal pyramidal neurons. J Neurosci 2002; 22: 8992-9004.
7. Chen K., Aradi I., Thon N., Eghbal-Ahmadi M., Baram TZ, Soltesz I.: Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability. Nat Med 2001; 7: 331-337.
8. Vilaine JP: The discovery of the selective If current inhibitor ivabradine (Procoralan): a new therapeutic approach to ischemic heart disease [in French]. Med Sci (Paris) 2006; 22: 87-94.
9. Stieber J., Wieland K., Stockl G., Ludwig A., Hofmann F.: Bradycardic and proarrhythmic properties of sinus node inhibitors. Mol Pharmacol 2006; 69: 1328-1337.
10. Vasilyev DV, Shan Q., Lee Y., Mayer SC, Bowlby MR, Strassle BW, et al: Direct inhibition of Ih by analgesic loperamide in rat DRG neurons. J Neurophysiol 2007; 97: 3713-3721.
11. Yao H., Donnelly DF, Ma C., LaMotte RH: Upregulation of the hyperpolarization-activated cation current after chronic compression of the dorsal root ganglion. J Neurosci 2003; 23: 2069-2074.
12. Vasylyev D., Lu Q., Bowlby M., Kaftan E., Shan Q.: Methods of identifying modulators of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. US/WO Patent Application 2008;WO/2008/121735.
13. Falconer M., Smith F., Surah-Narwal S., Congrave G., Liu Z., Hayter P., et al: High-throughput screening for ion channel modulators. J Biomol Screen 2002; 7: 460-465.
14. Gill S., Gill R., Lee SS, Hesketh JC, Fedida D., Rezazadeh S., et al: Flux assays in high throughput screening of ion channels in drug discovery. Assay Drug Dev Technol 2003; 1: 709-717.
15. Pan YP, Xu XH, Wang XL: High throughput screening method of potassium channel regulators [in Chinese]. Yao Xue Xue Bao 2004; 39: 85-88.
16. Parihar AS, Groebe DR, Scott VE, Feng J., Zhang XF, Warrior U., et al: Functional analysis of large conductance Ca2(+)-activated K(+) channels: ion flux studies by atomic absorption spectrometry. Assay Drug Dev Technol 2003; 1: 647-654.
17. Terstappen GC: Nonradioactive rubidium ion efflux assay and its applications in drug discovery and development. Assay Drug Dev Technol 2004; 2: 553-559.
18. Joesch C., Guevarra E., Pare SP, Bergner A., Zbinden P., Konrad D., et al: Use of FLIPR membrane potential dyes for validation of high-throughput screening with the FLIPR and microARCS technologies: identification of ion channel modulators acting on the GABA(A) receptor. J Biomol Screen 2008; 13: 218-228.
19. Whiteaker KL, Gopalakrishnan SM, Groebe D., Shieh CC, Warrior U., Burns DJ, et al: Validation of FLIPR membrane potential dye for high throughput screening of potassium channel modulators. J Biomol Screen 2001;6: 305-312.
20. Wolff C., Fuks B., Chatelain P.: Comparative study of membrane potentialsensitive fluorescent probes and their use in ion channel screening assays. J Biomol Screen 2003; 8: 533-543.
21. Xu J., Wang X., Ensign B., Li M., Wu L., Guia A., et al: Ion-channel assay technologies: quo vadis? Drug Discov Today 2001; 6: 1278-1287.
22. Lee YT, Vasilyev DV, Shan QJ, Dunlop J., Mayer S., Bowlby MR: Novel pharmacological activity of loperamide and CP-339,818 on human HCN channels characterized with an automated electrophysiology assay. Eur J Pharmacol 2008; 581: 97-104.
23. Vasilyev D., Lee Y., Shan Q., Kaftan E., Mayer S., Dunlop J., et al: Ion channel focused library: rationale and screening of HCN ion channel target. Paperpresented at the Ion Channel Targets: SelectBiosciences Conference, September 10-11, 2007, Boston.
24. Zhang JH, Chung TD, Oldenburg KR: A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 1999; 4: 67-73.
25. Schroeder K., Neagle B., Trezise DJ, Worley J.: Ionworks HT: a new highthroughput electrophysiology measurement platform. J Biomol Screen 2003; 8: 50-64.
26. Hamill OP, Marty A., Neher E., Sakmann B., Sigworth FJ: Improved patchclamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 1981; 391: 85-100.
27. Gill CH, Randall A., Bates SA, Hill K., Owen D., Larkman PM, et al: Characterization of the human HCN1 channel and its inhibition by capsazepine. Br J Pharmacol 2004; 143:411 -421.
28. Moosmang S., Stieber J., Zong X., Biel M., Hofmann F., Ludwig A.: Cellular expression and functional characterization of four hyperpolarizationactivated pacemaker channels in cardiac and neuronal tissues. Eur J Biochem 2001; 268: 1646-1652.
29. Yu X., Duan KL, Shang CF, Yu HG, Zhou Z.: Calcium influx through hyperpolarization-activated cation channels (I(h) channels) contributes to activityevoked neuronal secretion. Proc Natl Acad Sci USA 2004; 101: 1051-1056.
30. Arias RL, Bowlby MR: Pharmacological characterization of antiepileptic drugs and experimental analgesics on low magnesium-induced hyperexcitability in rat hippocampal slices. Brain Res 2005; 1047: 233-244.