Novel activation of non-selective cationic channels by dinitrosyl iron-thiosulfate in PC12 cells.
The Journal of Physiology. 2000-12-01; 529(3): 735-745
DOI: 10.1111/j.1469-7793.2000.00735.x
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1. J Physiol. 2000 Dec 15;529 Pt 3:735-45.
Novel activation of non-selective cationic channels by dinitrosyl
iron-thiosulfate in PC12 cells.
Giannone G(1), Takeda K, Kleschyov AL.
Author information:
(1)Universite Louis Pasteur de Strasbourg, CNRS UMR 7034, Pharmacologie et
Physico-Chimie des Interactions Cellulaires et Moleculaires, B.P. 24, 67401
Illkirch, France.
Erratum in
J Physiol 2001 Feb;530(3):575. Kleyschov AL [corrected to Kleschyov AL].
Low molecular mass dinitrosyl iron complexes (DNICs) are nitrosating agents and
it is known that the dinitrosyl iron moiety can be transferred to proteins. The
aim of the present study was to determine if the formation of protein-bound
dinitrosyl iron can modulate ionic channel activity. In PC12 cells, dinitrosyl
iron-thiosulfate (50 microM) caused irreversible activation of a depolarizing
inward current (IDNIC). IDNIC was partially inhibited by the metal chelator
diethyldithiocarbamate (DETC, 1 mM), but not by the reducing/denitrosylating
agent dithiothreitol (DTT, 5 mM). The activation of IDNIC was not reproduced by
application of nitric oxide (NO., 100 microM), S-nitrocysteine (200 microM) or
ferrous iron-thiosulfate (50 microM), and was not prevented by the irreversible
guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one (ODQ, 1
microM). Similarly, intracellular perfusion of dinitrosyl iron-thiosulfate (100
microM) did not result in activation of IDNIC. Ion replacement experiments show
that the DETC-sensitive component of IDNIC is a non-selective cationic current.
In accordance, IDNIC was blocked by antagonists of receptor-operated calcium
entry, gadolinium (25 microM) and SK&F 96365 (25 microM). Single-channel
measurements from outside-out patches reveal that the DETC-sensitive component of
IDNIC is an inward current carried by a cationic channel having a conductance of
50 pS. The present observations suggest that the formation of ion channel-bound
dinitrosyl iron represents another mechanism of regulation of ion channel
activity by NO.-related species, which may be particularly important in
pathophysiological processes where NO. is overproduced.
DOI: 10.1111/j.1469-7793.2000.00735.x
PMCID: PMC2270235
PMID: 11118502 [Indexed for MEDLINE]