Regulation of the human ether-a-gogo related gene (HERG) K+ channels by reactive oxygen species

Maurizio Taglialatela, Pasqualina Castaldo, Silvana Iossa, Anna Pannaccione, Angela Fresi, Eckhard Ficker, Lucio Annunziato

Research output: Contribution to journalArticle

Abstract

Human ether-a-gogo related gene (HERG) K+ channels are key elements in the control of cell excitability in both the cardiovascular and the central nervous systems. For this reason, the possible modulation by reactive oxygen species (ROS) of HERG and other cloned K+ channels expressed in Xenopus oocytes has been explored in the present study. Exposure of Xenopus oocytes to an extracellular solution containing FeSO4 (25-100 μM) and ascorbic acid (50-200 μM) (Fe/Asc) increased both malondialdehyde content and 2',7'- dichlorofluorescin fluorescence, two indexes of ROS production. Oocyte perfusion with Fe/Asc caused a 50% increase of the outward K+ currents carried by HERG channels, whereas inward currents were not modified. This ROS-induced increase in HERG outward K+ currents was due to a depolarizing shift of the voltage-dependence of channel inactivation, with no change in channel activation. No effect of Fe/Asc was observed on the expressed K+ currents carried by other K+ channels such as bEAG, rDRK1, and mIRK1. Fe/Asc-induced stimulation of HERG outward currents was completely prevented by perfusion of the oocytes with a ROS scavenger mixture (containing 1,000 units/ml catalase, 200 ng/ml superoxide dismutase, and 2 mM mannitol). Furthermore, the scavenger mixture also was able to reduce HERG outward currents in resting conditions by 30%, an effect mimicked by catalase alone. In conclusion, the present results seem to suggest that changes in ROS production can specifically influence K+ currents carried by the HERG channels.

Original languageEnglish
Pages (from-to)11698-11703
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number21
DOIs
Publication statusPublished - Oct 14 1997

ASJC Scopus subject areas

  • Genetics
  • General

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