Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

How to Fluorescently Label the Potassium Channel: A Case in hERG

Author(s): Xiaomeng Zhang, Beilei Wang, Zhenzhen Liu, Yubin Zhou and Lupei Du*

Volume 27 , Issue 18 , 2020

Page: [3046 - 3054] Pages: 9

DOI: 10.2174/0929867326666181129094455

Price: $65


hERG (Human ether-a-go-go-related gene) potassium channel, which plays an essential role in cardiac action potential repolarization, is responsible for inherited and druginduced long QT syndrome. Recently, the Cryo-EM structure capturing the open conformation of hERG channel was determined, thus pushing the study on hERG channel at 3.8 Å resolution. This report focuses primarily on summarizing the design rationale and application of several fluorescent probes that target hERG channels, which enables dynamic and real-time monitoring of potassium pore channel affinity to further advance the understanding of the channels.

Keywords: hERG channel, small molecule fluorescent probe, turn-on switch, fluorophore, recognition motif, Cryo- EM structure.

Zhou, Z.; Gong, Q.; Ye, B.; Fan, Z.; Makielski, J.C.; Robertson, G.A.; January, C.T. Properties of HERG channels stably expressed in HEK 293 cells studied at physiological temperature. Biophys. J., 1998, 74(1), 230-241.
[] [PMID: 9449325]
Ficker, E.; Thomas, D.; Viswanathan, P.C.; Dennis, A.T.; Priori, S.G.; Napolitano, C.; Memmi, M.; Wible, B.A.; Kaufman, E.S.; Iyengar, S.; Schwartz, P.J.; Rudy, Y.; Brown, A.M. Novel characteristics of a misprocessed mutant HERG channel linked to hereditary long QT syndrome. Am. J. Physiol. Heart Circ. Physiol., 2000, 279(4), H1748-H1756.
[] [PMID: 11009462]
He, F.Z.; McLeod, H.L.; Zhang, W. Current pharmacogenomic studies on hERG potassium channels. Trends Mol. Med., 2013, 19(4), 227-238.
[] [PMID: 23369369]
Hausammann, G.J.; Grütter, M.G. Chimeric hERG channels containing a tetramerization domain are functional and stable. Biochemistry, 2013, 52(51), 9237-9245.
[] [PMID: 24325597]
Sheykhansari, S.; Kozielski, K.; Bill, J.; Sitti, M.; Gemmati, D.; Zamboni, P.; Singh, A.V. Redox metals homeostasis in multiple sclerosis and amyotrophic lateral sclerosis: a review. Cell Death Dis., 2018, 9(3), 348.
[] [PMID: 29497049]
Tisato, V.; Zuliani, G.; Vigliano, M.; Longo, G.; Franchini, E.; Secchiero, P.; Zauli, G.; Paraboschi, E.M.; Vikram Singh, A.; Serino, M.L.; Ortolani, B.; Zurlo, A.; Bosi, C.; Greco, A.; Seripa, D.; Asselta, R.; Gemmati, D.; Gemmati, D. Gene-gene interactions among coding genes of iron-homeostasis proteins and APOE-alleles in cognitive impairment diseases. PLoS One, 2018, 13(3)e0193867
[] [PMID: 29518107]
Sanguinetti, M.C.; Tristani-Firouzi, M. hERG potassium channels and cardiac arrhythmia. Nature, 2006, 440(7083), 463-469.
[] [PMID: 16554806]
Grilo, L.S.; Carrupt, P.A.; Abriel, H. Stereoselective Inhibition of the hERG1 potassium channel. Front. Pharmacol., 2010, 1(137), 137.
[] [PMID: 21833176]
Bannister, J.P.; Chanda, B.; Bezanilla, F.; Papazian, D.M. Optical detection of rate-determining ion-modulated conformational changes of the ether-à-go-go K+ channel voltage sensor. Proc. Natl. Acad. Sci. USA, 2005, 102(51), 18718-18723.
[] [PMID: 16339906]
Gillie, D.J.; Novick, S.J.; Donovan, B.T.; Payne, L.A.; Townsend, C. Development of a high-throughput electrophysiological assay for the human ether-à-go-go related potassium channel hERG. J. Pharmacol. Toxicol. Methods, 2013, 67(1), 33-44.
[] [PMID: 23103595]
Zhou, Z.; Gong, Q.; January, C.T. Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome. Pharmacological and temperature effects. J. Biol. Chem., 1999, 274(44), 31123-31126.
[] [PMID: 10531299]
Di Martino, G.P.; Masetti, M.; Ceccarini, L.; Cavalli, A.; Recanatini, M. An automated docking protocol for hERG channel blockers. J. Chem. Inf. Model., 2013, 53(1), 159-175.
[] [PMID: 23259741]
Schmidtke, P.; Ciantar, M.; Theret, I.; Ducrot, P. Dynamics of hERG closure allow novel insights into hERG blocking by small molecules. J. Chem. Inf. Model., 2014, 54(8), 2320-2333.
[] [PMID: 25000969]
Brown, A.M. Drugs, hERG and sudden death. Cell Calcium, 2004, 35(6), 543-547.
[] [PMID: 15110144]
Du, L.; Li, M.; You, Q.; Xia, L. A novel structure-based virtual screening model for the hERG channel blockers. Biochem. Biophys. Res. Commun., 2007, 355(4), 889-894.
[] [PMID: 17331468]
Hancox, J.C.; James, A.F. Refining insights into high-affinity drug binding to the human ether-à-go-go-related gene potassium channel. Mol. Pharmacol., 2008, 73(6), 1592-1595.
[] [PMID: 18381562]
Smith, G.A.; Tsui, H.W.; Newell, E.W.; Jiang, X.; Zhu, X.P.; Tsui, F.W.; Schlichter, L.C. Functional up-regulation of HERG K+ channels in neoplastic hematopoietic cells. J. Biol. Chem., 2002, 277(21), 18528-18534.
[] [PMID: 11893742]
Bianchi, L.; Wible, B.; Arcangeli, A.; Taglialatela, M.; Morra, F.; Castaldo, P.; Crociani, O.; Rosati, B.; Faravelli, L.; Olivotto, M.; Wanke, E. herg encodes a K+ current highly conserved in tumors of different histogenesis: a selective advantage for cancer cells? Cancer Res., 1998, 58(4), 815-822.
[PMID: 9485040]
Babcock, J.J.; Li, M. hERG channel function: beyond long QT. Acta Pharmacol. Sin., 2013, 34(3), 329-335.
[] [PMID: 23459091]
Wang, W.; MacKinnon, R. Cryo-EM structure of the open human ether-a-go-go-related K+ channel hERG. Cell, 2017, 169(3), 422-430. e410
[] [PMID: 28431243]
Chen, S.Z.; Jiang, M.; Zhen, Y.S. HERG K+ channel expression-related chemosensitivity in cancer cells and its modulation by erythromycin. Cancer Chemother. Pharmacol., 2005, 56(2), 212-220.
[] [PMID: 15812674]
Mizukami, S.; Hori, Y.; Kikuchi, K. Small-molecule-based protein-labeling technology in live cell studies: probe-design concepts and applications. Acc. Chem. Res., 2014, 47(1), 247-256.
[] [PMID: 23927788]
Cristea, I.M.; Williams, R.; Chait, B.T.; Rout, M.P. Fluorescent proteins as proteomic probes. Mol. Cell. Proteomics, 2005, 4(12), 1933-1941.
[] [PMID: 16155292]
Sasano, T.; Ueda, K.; Orikabe, M. Hirano. Y.; Kawano, S.; Yasunami, M.; Isobe, M.; Kimura, A.; Hiraoka, M. Novel C-terminus frameshift mutation, 1122fs/147, of HERG in LQT2: additional amino acids generated by frameshift cause accelerated inactivation. J. Mol. Cell Cardiol, 2004, 37(6), 1205-11.
[] [PMID: 15572050] [] [PMID: 11780139]
Gustina, A.S.; Trudeau, M.C. A recombinant N-terminal domain fully restores deactivation gating in N-truncated and long QT syndrome mutant hERG potassium channels. Proc. Natl. Acad. Sci. U.S.A., 2009, 106(31), 13082-13087.
[PMID: 19651618]
Appeltant, R.; Maes, D.; Van Soom, A. Method for collecting and immobilizing individual cumulus cells enabling quantitative immunofluorescence analysis of proteins. Anal. Biochem., 2015, 480, 31-33.
[] [PMID: 25862082]
Robertson, D.; Savage, K.; Reis-Filho, J.S.; Isacke, C.M. Multiple immunofluorescence labelling of formalin-fixed paraffin-embedded (FFPE) tissue. BMC Cell Biol., 2008, 9(13), 13.
[] [PMID: 18366689]
Trimarchi, C.V.; Debbie, J.G. Standardization and quantitation of immunofluorescence in the rabies fluorescent-antibody test. Appl. Microbiol., 1972, 24(4), 609-612.
[] [PMID: 4564045]
Su, X.; Young, E.W.; Underkofler, H.A.; Kamp, T.J.; January, C.T.; Beebe, D.J. Microfluidic cell culture and its application in high-throughput drug screening: cardiotoxicity assay for hERG channels. J. Biomol. Screen., 2011, 16(1), 101-111.
[] [PMID: 21131594]
Mölne, J.; Breimer, M.E.; Svalander, C.T. Immunoperoxidase versus immunofluorescence in the assessment of human renal biopsies. Am. J. Kidney Dis., 2005, 45(4), 674-683.
[] [PMID: 15806470]
Es-Salah-Lamoureux, Z.; Fougere, R.; Xiong, P.Y.; Robertson, G.A.; Fedida, D. Fluorescence-tracking of activation gating in human ERG channels reveals rapid S4 movement and slow pore opening. PLoS One, 2010, 5(5)e10876
[] [PMID: 20526358]
Tristani-Firouzi, M.; Chen, J.; Sanguinetti, M.C. Interactions between S4-S5 linker and S6 transmembrane domain modulate gating of HERG K+ channels. J. Biol. Chem., 2002, 277(21), 18994-19000.
[] [PMID: 11864984]
Perry, M.D.; Ng, C.A.; Mann, S.A.; Sadrieh, A.; Imtiaz, M.; Hill, A.P.; Vandenberg, J.I. Getting to the heart of hERG K(+) channel gating. J. Physiol., 2015, 593(12), 2575-2585.
[] [PMID: 25820318]
Smith, P.L.; Yellen, G. Fast and slow voltage sensor movements in HERG potassium channels. J. Gen. Physiol., 2002, 119(3), 275-293.
[] [PMID: 11865022]
Vendrell, M.; Zhai, D.; Er, J.C.; Chang, Y.T. Combinatorial strategies in fluorescent probe development. Chem. Rev., 2012, 112(8), 4391-4420.
[] [PMID: 22616565]
Chan, J.; Dodani, S.C.; Chang, C.J. Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. Nat. Chem., 2012, 4(12), 973-984.
[] [PMID: 23174976]
Wang, B.; Liu, Z.; Ma, Z.; Li, M.; Du, L. Astemizole derivatives as fluorescent probes for hERG potassium channel imaging. ACS Med. Chem. Lett., 2016, 7(3), 245-249.
[] [PMID: 26985309]
Singleton, D.H.; Boyd, H.; Steidl-Nichols, J.V.; Deacon, M.; Groot, M.J.; Price, D.; Nettleton, D.O.; Wallace, N.K.; Troutman, M.D.; Williams, C.; Boyd, J.G. Fluorescently labeled analogues of dofetilide as high-affinity fluorescence polarization ligands for the human ether-a-go-go-related gene (hERG) channel. J. Med. Chem., 2007, 50(13), 2931-2941.
[] [PMID: 17536794]
Liu, Z.; Wang, B.; Ma, Z.; Zhou, Y.; Du, L.; Li, M. Fluorogenic probe for the human Ether-a-Go-Go-Related Gene potassium channel imaging. Anal. Chem., 2015, 87(5), 2550-2554.
[] [PMID: 25665091]
Liu, Z.; Jiang, T.; Wang, B.; Ke, B.; Zhou, Y.; Du, L.; Li, M. Environment-sensitive fluorescent probe for the human ether-a-go-go-related gene potassium channel. Anal. Chem., 2016, 88(3), 1511-1515.
[] [PMID: 26730746]
Liu, T.; Jiang, Y.; Liu, Z.; Li, J.; Fang, K.; Zhuang, C.; Du, L.; Fang, H.; Sheng, C.; Li, M. Environment-sensitive turn-on fluorescent probes for p53-MDM2 protein-protein interaction. MedChemComm, 2017, 8(8), 1668-1672.
[] [PMID: 30108877]
Dwivedi, C.; Pandey, I.; Pandey, H.; Patil, S.; Mishra, S.B.; Pandey, A.C.; Zamboni, P.; Ramteke, P.W.; Singh, A.V. In vivo diabetic wound healing with nanofibrous scaffolds modified with gentamicin and recombinant human epidermal growth factor. J. Biomed. Mater. Res. A, 2018, 106(3), 641-651.
[] [PMID: 28986947]
Singh, A.V.; Jahnke, T.; Kishore, V.; Park, B-W.; Batuwangala, M.; Bill, J.; Sitti, M. Cancer cells biomineralize ionic gold into nanoparticles-microplates via secreting defense proteins with specific gold-binding peptides. Acta Biomater., 2018, 71, 61-71.
[] [PMID: 29499399]
Reilly, D.T.; Kim, S.H.; Katzenellenbogen, J.A.; Schroeder, C.M. Fluorescent Nanoconjugate Derivatives with Enhanced Photostability for Single Molecule Imaging. Anal. Chem., 2015, 87(21), 11048-11057.
[] [PMID: 26461122]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy