1. Biel, M., Ludwig, A., Zong, X., et al. Hyperpolarization-Activated Cation Channels: A Multi-Gene Family. Rev. Physiol. Biochem. Pharmacol. 1999, 136, 165–181.
Google Scholar | Crossref | Medline2. Kaupp, U. B., Seifert, R. Molecular Diversity of Pacemaker Ion Channels. Annu. Rev. Physiol. 2001, 63, 235–257.
Google Scholar | Crossref | Medline3. Ludwig, A., Budde, T., Stieber, J., et al. Absence Epilepsy and Sinus Dysrhythmia in Mice Lacking the Pacemaker Channel HCN2. EMBO J. 2003, 22, 216–224.
Google Scholar | Crossref | Medline4. Santoro, B., Tibbs, G. R. The HCN Gene Family: Molecular Basis of the Hyperpolarization-Activated Pacemaker Channels. Ann. N.Y. Acad. Sci. 1999, 868, 741–764.
Google Scholar | Crossref | Medline5. Benarroch, E. E. HCN Channels: Function and Clinical Implications. Neurology 2013, 80, 304–310.
Google Scholar | Crossref | Medline6. DiFrancesco, D. Characterization of Single Pacemaker Channels in Cardiac Sino-Atrial Node cells. Nature 1986, 324, 470–473.
Google Scholar | Crossref | Medline7. DiFrancesco, D. The Role of the Funny Current in Pacemaker Activity. Circ. Res. 2010, 106, 434–446.
Google Scholar | Crossref | Medline8. Robinson, R. B., Siegelbaum, S. A. Hyperpolarization-Activated Cation Currents: From Molecules to Physiological Function. Annu. Rev. Physiol. 2003, 65, 453–480.
Google Scholar | Crossref | Medline9. Wahl-Schott, C., Biel, M. HCN Channels: Structure, Cellular Regulation and Physiological Function. Cell. Mol. Life Sci. 2009, 66, 470–494.
Google Scholar | Crossref | Medline10. Sartiani, L., Mannaioni, G., Masi, A., et al. The Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: From Biophysics to Pharmacology of a Unique Family of Ion Channels. Pharmacol. Rev. 2017, 69, 354–395.
Google Scholar | Crossref | Medline11. Zhuang, Q. X., Li, G. Y., Li, B., et al. Regularizing Firing Patterns of Rat Subthalamic Neurons Ameliorates Parkinsonian Motor Deficits. J. Clin. Invest. 2018, 128, 5413–5427.
Google Scholar | Crossref | Medline12. Raghunathan, S., Islas, J. F., Mistretta, B., et al. Conversion of Human Cardiac Progenitor Cells into Cardiac Pacemaker-Like Cells. J. Mol. Cell. Cardiol. 2019, 138, 12–22.
Google Scholar | Crossref | Medline13. Santoro, B., Shah, M. M. Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels as Drug Targets for Neurological Disorders. Annu. Rev. Pharmacol. Toxicol. 2020, 60, 109–131.
Google Scholar | Crossref | Medline14. Andrikopoulos, G., Dasopoulou, C., Sakellariou, D., et al. Ivabradine: A Selective If Current Inhibitor in the Treatment of Stable Angina. Recent Pat. Cardiovasc. Drug Discov. 2006, 1, 277–282.
Google Scholar | Crossref | Medline15. Cargnoni, A., Ceconi, C., Stavroula, G., et al. Heart Rate Reduction by Pharmacological If Current Inhibition. Adv. Cardiol. 2006, 43, 31–44.
Google Scholar | Crossref | Medline16. Fox, K., Ford, I., Steg, P. G., et al. Ivabradine for Patients with Stable Coronary Artery Disease and Left-Ventricular Systolic Dysfunction (BEAUTIFUL): A Randomised, Double-Blind, Placebo-Controlled Trial. Lancet 2008, 372, 807–816.
Google Scholar | Crossref | Medline17. Swedberg, K., Komajda, M., Bohm, M., et al. Ivabradine and Outcomes in Chronic Heart Failure (SHIFT): A Randomised Placebo-Controlled Study. Lancet 2010, 376, 875–885.
Google Scholar | Crossref | Medline18. BoSmith, R. E., Briggs, I., Sturgess, N. C. Inhibitory Actions of ZENECA ZD7288 on Whole-Cell Hyperpolarization Activated Inward Current (If) in Guinea-Pig Dissociated Sinoatrial Node Cells. Br. J. Pharmacol. 1993, 110, 343–349.
Google Scholar | Crossref | Medline19. He, J. T., Li, X. Y., Zhao, X., et al. Hyperpolarization-Activated and Cyclic Nucleotide-Gated Channel Proteins as Emerging New Targets in Neuropathic Pain. Rev. Neurosci. 2019, 30, 639–649.
Google Scholar | Crossref | Medline20. Cao, Y., Chen, S., Liang, Y., et al. Inhibition of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels by Beta-Blocker Carvedilol. Br. J. Pharmacol. 2018, 175, 3963–3975.
Google Scholar | Crossref | Medline21. Tamura, A., Ogura, T., Uemura, H., et al. Effects of Antiarrhythmic Drugs on the Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Current. J. Pharmacol. Sci. 2009, 110, 150–159.
Google Scholar | Crossref | Medline22. Cao, Y., Pang, J., Zhou, P. HCN Channel as Therapeutic Targets for Heart Failure and Pain. Curr. Topics Med. Chem. 2016, 16, 1855–1861.
Google Scholar | Crossref | Medline23. Bucchi, A., Tognati, A., Milanesi, R., et al. Properties of Ivabradine-Induced Block of HCN1 and HCN4 Pacemaker Channels. J. Physiol. 2006, 572, 335–346.
Google Scholar | Crossref | Medline24. Thollon, C., Bedut, S., Villeneuve, N., et al. Use-Dependent Inhibition of hHCN4 by Ivabradine and Relationship with Reduction in Pacemaker Activity. Br. J. Pharmacol. 2007, 150, 37–46.
Google Scholar | Crossref | Medline25. Shin, K. S., Rothberg, B. S., Yellen, G. Blocker State Dependence and Trapping in Hyperpolarization-Activated Cation Channels: Evidence for an Intracellular Activation Gate. J. Gen. Physiol. 2001, 117, 91–101.
Google Scholar | Crossref | Medline26. Meng, Q. T., Xia, Z. Y., Liu, J., et al. Local Anesthetic Inhibits Hyperpolarization-Activated Cationic Currents. Mol. Pharmacol. 2011, 79, 866–873.
Google Scholar | Crossref | Medline27. Farre, C., Stoelzle, S., Haarmann, C., et al. Automated Ion Channel Screening: Patch Clamping Made Easy. Expert Opin. Ther. Targets 2007, 11, 557–565.
Google Scholar | Crossref | Medline28. McManus, O. B. HTS Assays for Developing the Molecular Pharmacology of Ion Channels. Curr. Opin. Pharmacol. 2014, 15, 91–96.
Google Scholar | Crossref | Medline29. Milligan, C. J., Moller, C. Automated Planar Patch-Clamp. Methods Mol. Biol. 2013, 998, 171–187.
Google Scholar | Crossref | Medline30. Priest, B. T., Cerne, R., Krambis, M. J., et al. Automated Electrophysiology Assays. In Assay Guidance Manual; Sittampalam, G. S., Grossman, A., Brimacombe, K., et al., Eds.; Eli Lilly & Company and the National Center for Advancing Translational Sciences: Bethesda, MD, 2004.
Google Scholar31. Harmer, A. R., Abi-Gerges, N., Easter, A., et al. Optimisation and Validation of a Medium-Throughput Electrophysiology-Based hNav1.5 Assay Using IonWorks. J. Pharmacol. Toxicol. Methods 2008, 57, 30–41.
Google Scholar | Crossref | Medline32. Trivedi, S., Dekermendjian, K., Julien, R., et al. Cellular HTS Assays for Pharmacological Characterization of Na(V)1.7 Modulators. Assay Drug Dev. Technol. 2008, 6, 167–179.
Google Scholar | Crossref | Medline33. Obergrussberger, A., Brüggemann, A., Goetze, T. A., et al. Automated Patch Clamp Meets High-Throughput Screening: 384 Cells Recorded in Parallel on a Planar Patch Clamp Module. J. Lab. Autom. 2016, 21, 779–793.
Google Scholar | SAGE Journals34. Bell, D. C., Dallas, M. L. Using Automated Patch Clamp Electrophysiology Platforms in Pain-Related Ion Channel Research: Insights from Industry and Academia. Br. J. Pharmacol. 2018, 175, 2312–2321.
Google Scholar | Crossref | Medline35. Obergrussberger, A., Goetze, T. A., Brinkwirth, N., et al. An Update on the Advancing High-Throughput Screening Techniques for Patch Clamp-Based Ion Channel Screens: Implications for Drug Discovery. Expert Opin. Drug Discov. 2018, 13, 269–277.
Google Scholar | Crossref | Medline36. Walsh, K. B. Screening Technologies for Inward Rectifier Potassium Channels: Discovery of New Blockers and Activators. SLAS Discov. 2020, 25, 420–433.
Google Scholar | Abstract37. Obergrussberger, A., Friis, S., Brüggemann, A., et al. Automated Patch Clamp in Drug Discovery: Major Breakthroughs and Innovation in the Last Decade. Expert Opin. Drug Discov. 2021, 16, 1–5.
Google Scholar | Crossref | Medline38. Schroeder, K., Neagle, B., Trezise, D. J., et al. IonWorks HT: A New High-Throughput Electrophysiology Measurement Platform. J. Biomol. Screen. 2003, 8, 50–64.
Google Scholar | SAGE Journals39. Goehring, A., Lee, C. H., Wang, K. H., et al. Screening and Large-Scale Expression of Membrane Proteins in Mammalian Cells for Structural Studies. Nat. Protoc. 2014, 9, 2574–2585.
Google Scholar | Crossref | Medline40. Wright, P. D., Kanumilli, S., Tickle, D., et al. A High-Throughput Electrophysiology Assay Identifies Inhibitors of the Inwardly Rectifying Potassium Channel Kir7.1. J. Biomol. Screen. 2015, 20, 739–747.
Google Scholar | SAGE Journals41. Ludwig, A., Zong, X., Stieber, J., et al. Two Pacemaker Channels from Human Heart with Profoundly Different Activation Kinetics. EMBO J. 1999, 18, 2323–2329.
Google Scholar | Crossref | Medline42. Michels, G., Er, F., Khan, I., et al. Single-Channel Properties Support a Potential Contribution of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels and If to Cardiac Arrhythmias. Circulation 2005, 111, 399–404.
Google Scholar | Crossref | Medline43. Qu, J., Altomare, C., Bucchi, A., et al. Functional Comparison of HCN Isoforms Expressed in Ventricular and HEK 293 Cells. Pflugers Arch. 2002, 444, 597–601.
Google Scholar | Crossref | Medline44. Seifert, R., Scholten, A., Gauss, R., et al. Molecular Characterization of a Slowly Gating Human Hyperpolarization-Activated Channel Predominantly Expressed in Thalamus, Heart, and Testis. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 9391–9396.
Google Scholar | Crossref | Medline45. Wainger, B. J., DeGennaro, M., Santoro, B., et al. Molecular Mechanism of cAMP Modulation of HCN Pacemaker Channels. Nature 2001, 411, 805–810.
Google Scholar | Crossref | Medline46. Sanguinetti, M. C., Tristani-Firouzi, M. hERG Potassium Channels and Cardiac Arrhythmia. Nature 2006, 440, 463–469.
Google Scholar | Crossref | Medline47. Vandenberg, J. I., Perry, M. D., Perrin, M. J., et al. hERG K(+) Channels: Structure, Function, and Clinical Significance. Physiol. Rev. 2012, 92, 1393–1478.
Google Scholar | Crossref | Medline48. Perry, M., Stansfeld, P. J., Leaney, J., et al. Drug Binding Interactions in the Inner Cavity of HERG Channels: Molecular Insights from Structure-Activity Relationships of Clofilium and Ibutilide Analogs. Mol. Pharmacol. 2006, 69, 509–519.
Google Scholar | Crossref | Medline49. Stansfeld, P. J., Gedeck, P., Gosling, M., et al. Drug Block of the hERG Potassium Channel: Insight from Modeling. Proteins 2007, 68, 568–580.
Google Scholar | Crossref | Medline50. Bucchi, A., Baruscotti, M., Nardini, M., et al. Identification of the Molecular Site of Ivabradine Binding to HCN4 Channels. PLoS One 2013, 8, e53132.
Google Scholar | Crossref | Medline51. Finkel, A., Wittel, A., Yang, N., et al. Population Patch Clamp Improves Data Consistency and Success Rates in the Measurement of Ionic Currents. J. Biomol. Screen. 2006, 11, 488–496.
Google Scholar | SAGE Journals