"Janus face" of nitric oxide action on plasma membrane and intracellular ionic channels

M. Taglialatela, A. Pannaccione, M. Cataldi, P. Castaldo, A. Secondo, S. Iossa, G. F. Di Renzo, L. Annunziato

Research output: Contribution to journalArticlepeer-review


This paper focused on the role played by nitric oxide free radical (NO·) on different ion channels involved in the progression of brain ischemia and several neurodegenerative diseases. We reviewed the available evidence suggesting that NO· modulates glutamate-operated channels, Na+-, Ca2+- and K+-channels. A special emphasis has been directed to the voltage dependent K+-channel (product of the human ether-a-gogo related gene: hERG) which had extensively been studied in our laboratory. We have shown that the inhibition of nitric oxide synthase (NOS) by L-NG-Nitroarginine methyl ester (L-NAME) (0.03-3.0 mM) dose-dependently suppresses the outward currents carried by the hERG K+-channels expressed in Xenopus oocytes, whereas the increase in NO· levels achieved by exposure to L-arginine (0.03-10.0 mM) inhibits these currents. Similar results were obtained using four NO· donors belonging to different chemical classes, such as sodium-nitroprussiate (SNP) (1-1000 μM), 3-morpholino-sydnonimine (SIN-1) (100-1000 μM), DiethylenetetramineNONOate (NOC-18) (1-300 μM), and S-nitroso-N-acetylpenicillamine (SNAP) (1-300 μM). The inhibitory effect of NO·-donors on hERG K+-channels was prevented by the NO·-scavengers 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) and hemoglobin. One mM 8-Br-cGMP, a membrane permeable analogue of cGMP, failed to reproduce the inhibitory action of NO·-donors on hERG K+-dependent outward currents, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (50 μM), a specific inhibitor of the NO·-dependent guanylyl cyclase, did not interfere with outward hERG K+ currents and did not prevent their inhibition by 0.3 mM NOC-18. Evidence suggesting that NO·-action on hERG-K+-channels is dependent on the reactive oxygen species (ROS) scavenging effect of this gas has been presented.

Original languageEnglish
Pages (from-to)379-394
Number of pages16
JournalArchives of Gerontology and Geriatrics
Issue numberSUPPL.
Publication statusPublished - 2001


  • hERG gene
  • Ionic channels
  • Ischemia
  • Neurodegenerative disorders
  • Nitric oxide

ASJC Scopus subject areas

  • Ageing
  • Medicine(all)


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