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Peroxynitrite affects Ca 2+ influx through voltage‐dependent calcium channels
Author(s) -
Ohkuma Seitaro,
Katsura Masashi,
Higo Atsuko,
Shirotani Kenji,
Hara Atsuo,
Tarumi Chihaya,
Ohgi Tadaaki
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00045.x
Subject(s) - chemistry , peroxynitrite , biophysics , calcium , voltage dependent calcium channel , depolarization , membrane potential , pharmacology , biochemistry , biology , organic chemistry , enzyme , superoxide
The effect of peroxynitrite (OONO − ) on voltage‐dependent Ca 2+ channels (VDCCs) was examined by measuring [ 45 Ca 2+ ] influx into mouse cerebral cortical neurones. OONO − time‐ and dose‐dependently increased [ 45 Ca 2+ ] influx and this increase was abolished by manganese (III) tetrakis (4‐benzoic acid) porphyrin, a scavenger for OONO − . Inhibition of cyclic GMP (cGMP) formation did not alter the OONO − ‐induced [ 45 Ca 2+ ] influx. OONO − , as well as 30 m m KCl, significantly increased fluorescence intensity of cell‐associated bis ‐(1,3‐dibutylbarbituric acid) trimethine oxonol ( bis ‐oxonol). Tetrodotoxin and membrane stabilizers such as lidocaine dose‐dependently suppressed OONO − ‐induced [ 45 Ca 2+ ] influx. Although each of 1 µ m nifedipine and 1 µ m ω‐agatoxin VIA (ω‐ATX) significantly inhibited the OONO − ‐induced [ 45 Ca 2+ ] influx and the concomitant presence of these agents completely abolished the influx, 1 µ m ω‐conotoxin GVIA (ω‐CTX) showed no effect on the influx. On the other hand, OONO − itself reduced 30 m m KCl‐induced [ 45 Ca 2+ ] influx to the level of [ 45 Ca 2+ ] influx induced by OONO − alone, and the magnitude of this reduction was as same as that of KCl‐induced [ 45 Ca 2+ ] influx by ω‐CTX. These results indicate that OONO − increases [ 45 Ca 2+ ] influx into the neurones through opening P/Q‐ and L‐type VDCCs subsequent to depolarization, and inhibits the influx through N‐type VDCCs.