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

Citation
M. Taglialatela et al., "Janus face" of nitric oxide action on plasma membrane and intracellular ionic channels, ARCH GER G, 2001, pp. 379-394
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research General Topics
Journal title
ARCHIVES OF GERONTOLOGY AND GERIATRICS
ISSN journal
0167-4943 → ACNP
Year of publication
2001
Supplement
7
Pages
379 - 394
Database
ISI
SICI code
0167-4943(2001):<379:"FONOA>2.0.ZU;2-M
Abstract
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 s everal neurodegenerative diseases. We reviewed the available evidence sugge sting that NO. modulates glutamate-operated channels, Na+-, Ca2+- and K+-ch annels. A special emphasis has been directed to the voltage dependent K+-ch annel (product of the human ether-a-gogo related gene: hERG) which had exte nsively been studied in our laboratory. We have shown that the inhibition o f nitric oxide synthase (NOS) by L-N-G-Nitroarginine methyl ester (L-NAME) (0.03-3.0 mM) dose-dependently suppresses the outward currents carried by t he hERG K+-channels expressed in Xenopus oocytes, whereas the increase in N O. 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 muM ), 3-morpholino-sydnonimine (SIN-1) (100-1000 muM), DiethylenetetramineNONO ate (NOC-18) (1-300 muM), and S-nitroso-N-acetylpenicillamine (SNAP) (1-300 muM). The inhibitory effect of NO.-donors on hERG K+-channels was prevente d by the NO.-scavengers 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-ox ide (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 muM), 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 eff ect of this gas has been presented.