Abstract
Ether‐à‐go‐go‐related gene (erg) channels are voltage‐dependent K+ channels mediating inward‐rectifying K+ currents because of their peculiar gating kinetics. These characteristics are essential for repolarization of the cardiac action potential. Inherited and acquired malfunctioning of erg channels may lead to the long QT‐syndrome. However, erg currents have also been recorded in many other excitable cells, like smooth muscle fibres of the gastrointestinal tract, neuroblastoma cells or neuroendocrine cells. In these cells erg currents contribute to the maintenance of the resting potential. Changes in the resting potential are related to cell‐specific functions like increase in hormone secretion, frequency adaptation or increase in contractility.
Keywords: ether‐à‐go‐go‐related gene K+ channel, HERG‐inward rectifier, heart action potential, long QT syndrome, resting potential, depolarization, prolactin secretion
References
- 1. Schwarz J.R., Bauer C.K., The ether‐à‐go‐go‐related gene K+ current: Functions of a strange inward rectifier, News Physiol. Sci., 14: 135–142, 1999. [DOI] [PubMed] [Google Scholar]
- 2. Bauer C.K., Schwarz J.R., Physiology of EAG K+ channels. Topical Review. J. Membrane Biol., 182: 1–15, 2001. [DOI] [PubMed] [Google Scholar]
- 3. Warmke J.W., Ganetzky B., A family of potassium channel genes related to eag in Drosophila and mammals, Proc. Natl. Acad. Sci. USA, 91: 3438–3442, 1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Bauer C.K., Engeland B., Wulfsen I., Ludwig J., Pongs O., Schwarz J.R., RERG is a molecular correlate of the inward‐rectifying K+ current in clonal rat pituitary cells, Receptors Channels, 6: 19–29, 1998. [PubMed] [Google Scholar]
- 5. Shi W., Wymore R.S. Wang H.‐S., Pan Z., Cohen I.S. McKinnon D., Dixon J.E., Identification of two nervous system‐specific members of the erg potassium channel gene family, J. Neurosci., 17: 9423–9432, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Bauer C.K., Wulfsen I., Schäfer R., Glassmeier G., Wimmers S., Flitsch J., Lüdecke D.K., Schwarz J.R., HERG K+ currents in human prolactin‐secreting adenoma cells, Pflügers Arch., 445: 589–600, 2003. [DOI] [PubMed] [Google Scholar]
- 7. Marais‐Cabral J.H., Lee A., Cohen S.L., Chait B.T., Li M., MacKinnon R., Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain, Cell, 95: 649–655, 1998. [DOI] [PubMed] [Google Scholar]
- 8. Schönherr R., Heinemann S., Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel, J. Physiol., 493: 635–642, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Snyders D.J., Chaudhary A., High affinity open channel block by dofetilide of HERG expressed in a human cell line, Mol. Pharmacol., 49: 949–955, 1996. [PubMed] [Google Scholar]
- 10. Shibasaki T., Conductance and kinetics of delayed rectifier potassium channels in nodal cells of the rabbit heart, J. Physiol., 387: 227–250, 1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Trudeau M.C., Warmke J.W., Ganetzky B., Robertson G.A., HERG, a human inward rectifier in the voltage‐gated potassium channel family, Science, 269: 92–95, 1995. [DOI] [PubMed] [Google Scholar]
- 12. Smith P.L., Baukrowitz T., Yellen G., The inward rectification mechanism of the HERG cardiac potassium channel, Nature, 379: 833–836, 1996. [DOI] [PubMed] [Google Scholar]
- 13. Jan L.Y., Jan Y.N., Cloned potassium channels from eukaryotes and prokaryotes, Annu. Rev. Neurosci., 20: 91–123, 1997. [DOI] [PubMed] [Google Scholar]
- 14. Sanguinetti M.C., Jiang C., Curran M.E., Keating M.T., A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel, Cell, 81: 299–307, 1995. [DOI] [PubMed] [Google Scholar]
- 15. Gurrola G.B., Rosati B., Rocchetti M., Pimienta G., Zaza A., Arcangeli A., Olivotto M., Possani L.D., Wanke E., A toxin to nervous, cardiac, and endocrine ERG K+ channels isolated from Centruroides noxius scorpion venom, FASEB J., 13: 953–962, 1999. [PubMed] [Google Scholar]
- 16. Schledermann W., Wulfsen I., Schwarz J.R., Bauer C.K., Modulation of rat erg1, erg2, erg3 and HERG K+ currents by thyrotropin‐releasing hormone in anterior pituitary cells via the native signal cascade, J. Physiol., 532: 143–163, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Wimmers S., Wulfsen I., Bauer C.K., Schwarz J.R., Erg1, erg2 and erg3 K channel subunits are able to form heteromultimers, Pflügers Arch., 441: 450–455, 2001. [DOI] [PubMed] [Google Scholar]
- 18. Sanguinetti M.C., Jurkiewicz N.K., Two components of cardiac delayed rectifier K+ current, J. Gen. Physiol., 96: 195–215, 1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Zaza A., Micheletti M., Brioschi A., Rocchetti M., Ionic currents during sustained pacemaker activity in rabbit sino‐atrial myocytes, J. Physiol., 505: 677–688, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Liu S., Rasmusson R.L., Campbell D.L., Wang S., Strauss H.C., Activation and inactivation kinetics of an E‐4031‐sensitive current from single ferret atrial myocytes, Biophys. J., 70: 2704–2715, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Verheijck E.E., Van Ginneken A.C.G., Bourier J., Bouman L.N., Effects of delayed rectifier current blockage by E‐4031 on impulse generation in single sinuatrial nodal myocytes of the rabbit, Circ. Res., 76: 607–615, 1995. [DOI] [PubMed] [Google Scholar]
- 22. Curran M.E., Splawski I., Timothy K.W., Vincent G.M., Green E.D., Keating M.T., A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome, Cell, 80: 795–803, 1995. [DOI] [PubMed] [Google Scholar]
- 23. Sanguinetti M.C., Curran M.E., Spector P.S., Keating M.T., Spectrum of HERG K+‐channel dysfunction in an inherited cardiac arrhythmia, Proc. Natl. Acad. Sci. USA, 93: 2208–2212, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Abbott G.W., Sesti F., Splawski I., Buck M.E., Lehmann M.H., Timothy K.W., Keating M.T., Goldstein S.A.N., MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia, Cell, 97: 175–187, 1999. [DOI] [PubMed] [Google Scholar]
- 25. Sanguinetti M.C., Keating M.T., Role of delayed rectifier potassium channels in cardiac repolarization and arrhythmias, News Physiol. Sci., 12: 152–157, 1997. [Google Scholar]
- 26. Suessbrich H., Schönherr R., Heinemann S.H., Attali B., Lang F., Busch A.E., The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes, Brit. J. Pharmacol., 120: 968–974, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Suessbrich H., Waldegger S., Lang F., Busch A.E., Blockade of HERG channels expressed in Xenopus oocytes by the histamine receptor antagonists terfenadine and astemizole, FEBS Lett., 385: 77–80, 1996. [DOI] [PubMed] [Google Scholar]
- 28. Chouabe C., Drici M.‐D., Romey G., Barhanin J., Lazdunski M., HERG and KvLQT1/IsK, the cardiac K+ channels involved in long QT syndromes, are targets for calcium channel blockers, Mol. Pharmacol., 54: 695–703, 1998. [PubMed] [Google Scholar]
- 29. Mohammad S., Zhou Z., Gong Q., January C.T., Blockage of the HERG human cardiac K+ channel by the gastrointestinal prokinetic agent cisapride, Am. J. Physiol., 273: H2534–H2538, 1997. [DOI] [PubMed] [Google Scholar]
- 30. Rosati B., Rocchetti M., Zaza A., Wanke E., Sulfonylureas blockade of neural and cardiac HERG channels, FEBS Lett., 440: 125–130, 1998. [DOI] [PubMed] [Google Scholar]
- 31. Akbarali H.I., Thatte H., He X.D., Giles W.R., Goyal R.K., Role of HERG‐like K+ currents in opossum esophageal circular smooth muscle, Am. J. Physiol., 46: C1284–C1290, 1999. [DOI] [PubMed] [Google Scholar]
- 32. Ohya S., Asakura K., Muraki K., Watanabe M., Imaizumi Y., Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle, Am. J. Physiol. Gastrointest. Liver Physiol., 282: G277–G287, 2002. [DOI] [PubMed] [Google Scholar]
- 33. Shoeb F., Malykhina A.P., Akbarali H.I., Cloning and functional characterization of the smooth muscle ether‐ago‐go‐related gene K+ channel, J. Biol. Chem., 278: 2503–2514, 2003. [DOI] [PubMed] [Google Scholar]
- 34. Parr E., Pozo M.J., Horowitz B., Nelson M.T., Mawe G.M., ERG K+ channels modulate the elctrical and contractile activities of gallbladder smooth muscle, Am. J. Physiol. Gastrointest. Liver Physiol., 284: G392–G398, 2003. [DOI] [PubMed] [Google Scholar]
- 35. Overholt J.L., Ficker E., Yang T., Shams H., Bright G.R., Prabhakar N.R., HERG‐like potassium current regulates the resting the resting membrane potential in glomus cells of the rabbit carotid body, J. Neurophysiol., 83: 1150–1157, 2000. [DOI] [PubMed] [Google Scholar]
- 36. Pellequer J.‐L., Brudler R., Getzhoff E.D., Biological sensors: more than one way to sense oxygen, Curr. Biol., 9: R416–R418, 1999. [DOI] [PubMed] [Google Scholar]
- 37. Taglialatela M., Castaldo P., Iossa S., Pannaccione A., Fres A., Ficker E., Annunziato L., Regulation of the human ether‐a‐gogo related gene (HERG) K+ channels by reactive oxygen species, Proc. Natl. Acad. Sci. USA 94: 11698–11703, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Corrette B.J., Bauer C.K., Schwarz J.R., Electrophysiology of anterior pituitary cells In: The Electrophysiology of Neuroendocrine Cells. Scherübl H. and Hescheler J., editors, CRC Press, Boca Raton , 1995, pp. 101–143. [Google Scholar]
- 39. Bauer C.K., Meyerhof W., Schwarz J.R., An inwardrectifying K+ current in clonal rat pituitary cells and its modulation by thyrotrophin‐releasing hormone, J. Physiol. 429: 169–189, 1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Barros F., Delgado L.M., Del Camino D., de la Peña P., Characteristics and modulation by thyrotropin‐releasing hormone of an inwardly rectifying K+ current in patchperforrated GH3 anterior pituitary cells, Pflügers Arch. 422: 31–39, 1992. [DOI] [PubMed] [Google Scholar]
- 41. Corrette B.J., Bauer C.K., Schwarz J.R., An inactivating inward‐rectifying K+ current present in prolactin cells from the pituitary of lactating rats, J. Membrane Biol., 150: 185–195, 1996. [DOI] [PubMed] [Google Scholar]
- 42. Schäfer R., Wulfsen I., Behrens S., Weinsberg F., Bauer C.K., Schwarz J.R., The erg‐like potassium current in rat lactotrophs, J. Physiol., 518: 401–416, 1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43. Bauer C.K., The erg inwardly rectifying K+ current and its modulation by thyrotrophin‐releasing hormone in giant clonal rat anterior pituitary cells, J. Physiol., 510: 63–70, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44. Barros F., Mieskes G., Del Camino D., de la Peña P., Protein phosphatase 2A reverses inhibition of inward rectifying K+ currents by thyrotropin‐releasing hormone in GH3 pituitary cells, FEBS Lett., 336: 433–439, 1993. [DOI] [PubMed] [Google Scholar]
- 45. Bauer C.K., Davison I., Kubasov I., Schwarz J.R., Mason W.T., Different G proteins are involved in the biphasic response of clonal rat pituitary cells to thyrotropin releasing hormone, Pflügers Arch., 428: 17–25, 1994. [DOI] [PubMed] [Google Scholar]
- 46. Barros F., Gómez‐Varela D., Viloria C.G., Palomero T., Giráldez T., de la Peña P., Modulation of human erg K+ channel gating by activation of a G protein‐coupled receptor and protein kinase C , J. Physiol., 511: 333–346, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47. Bauer C.K., Schäfer R., Schiemann D., Reid G., Hanganu I., Schwarz J.R., A functional role of the erg‐like inward‐rectifying K+ current in prolactin secretion from rat lactotrophs, Mol. Cell. Endocrinol., 148: 37–45, 1999. [DOI] [PubMed] [Google Scholar]
- 48. Arcangeli A., Rosati B., Cherubini A., Crociani O., Fontana L., Ziller C., Wanke E., Olivotto M., HERG‐ and IRK‐like inward rectifier currents are sequentially expressed during neuronal development of neural crest cells and their derivatives, Eur. J. Neurosci., 9: 2596–2604, 1997. [DOI] [PubMed] [Google Scholar]
- 49. Arcangeli A., Bianchi L., Becchetti A., Faravelli L., Coronnello M., Mini E., Olivotto M., Wanke E., A novel inward‐rectifying K+ current with a cell‐cycle dependence governs the resting potential of mammalian neuroblastoma cells, J. Physiol., 489: 455–471, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50. Faravelli L., Arcangeli A., Olivotto M., Wanke E., A HERG‐like K+ channel in rat F‐11 DRG cell line: pharmacological identification and biophysical characterization, J. Physiol., 496: 13–23, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51. Meyer R., Heinemann S.H., Characterization of an eaglike potassium channel in human neuroblastoma cells, J. Physiol., 508: 49–56, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52. Arcangeli A., Becchetti A., Mannini A., Mugnai G., De Filippi P., Tarone G., del Bene M.R., Barletta E., Wanke E., Olivotto M., Integrin‐mediated neurite outgrowth in neuroblastoma cells depends on the activation of potassium channels, J. Cell Biol., 122: 1131–1143, 1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53. Arcangeli A., Faravelli L., Bianchi L., Rosati B., Gritti A., Vescovi A., Wanke E., Olivotto M., Soluble or bound laminin elicit in human neuroblastoma cells short‐ or longterm potentiation of a K+ inwardly rectifying current: relevance to neuritogenesis, Cell Adhes. Commun., 4: 369–385, 1996. [DOI] [PubMed] [Google Scholar]
- 54. Zhou W., Cayabyab F.S., Pennefather P.S., Schlichter L.C., DeCoursey T.E., HERG‐like K+ channels in microglia, J. Gen. Physiol., 111: 781–794, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55. 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., 58: 815–822, 1998. [PubMed] [Google Scholar]
- 56. Chiesa N., Rosati B., Arcangeli A., Olivotto M., Wanke, E. , A novel role for HERG K+ channels: spike‐frequency adaptation. J. Physiol. 501: 313–318, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57. Brown D.A., M currents In: Ion channels. Narahashi T., editor, Plenum Press, New York , London , 1988, pp. 55–94. [DOI] [PubMed] [Google Scholar]
- 58. Schönherr R., Rosati B., Hehl S., Rao V.G., Arcangeli A., Olivotto M., Heinemann S.H., Wanke E., Functional role of the slow activation property of ERG K+ channels. Eur. J. Neurosci. 11: 753–760, 1999. [DOI] [PubMed] [Google Scholar]
- 59. Saganich M.J., Machado E., Rudy B., Differential expression of genes encoding subthreshold‐operating voltage‐gated K+ channels in the brain. J. Neurosc. 21: 4609–4624, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
