ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
The effect of peroxynitrite (OONO−) on voltage-dependent Ca2+ channels (VDCCs) was examined by measuring [45Ca2+] influx into mouse cerebral cortical neurones. OONO− time- and dose-dependently increased [45Ca2+] 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 [45Ca2+] influx. OONO−, as well as 30 mm 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 [45Ca2+] influx. Although each of 1 µm nifedipine and 1 µmω-agatoxin VIA (ω-ATX) significantly inhibited the OONO−-induced [45Ca2+] influx and the concomitant presence of these agents completely abolished the influx, 1 µmω-conotoxin GVIA (ω-CTX) showed no effect on the influx. On the other hand, OONO− itself reduced 30 mm KCl-induced [45Ca2+] influx to the level of [45Ca2+] influx induced by OONO− alone, and the magnitude of this reduction was as same as that of KCl-induced [45Ca2+] influx by ω-CTX. These results indicate that OONO− increases [45Ca2+] influx into the neurones through opening P/Q- and L-type VDCCs subsequent to depolarization, and inhibits the influx through N-type VDCCs.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2001.00045.x
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