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| Nitric oxide promotes intracellular calcium release from mitochondria in striatal neurons |
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| Author(s): Horn TFW, Wolf G, Duffy S, Weiss S, Keilhoff G, MacVicar BA |
| Source: FASEB JOURNAL Volume: 16 Issue: 12 Pages: 1611-1622 Published: OCT 2002 |
| Times Cited: 34 References: 51 |
| Abstract: Overproduction of nitric oxide by NMDA receptor stimulation is implicated in calcium deregulation and neurodegeneration of striatal neurons. We investigated the involvement of nitric oxide (NO) in inducing intracellular calcium release and in modifying calcium transients evoked by NMDA. NO application (4-10 muM) reversibly and repeatedly increased the intracellular calcium concentration [Ca2+](i) in Fura-2- or fluo-3-loaded cultured mouse striatal neurons. NO-induced [Ca2+](i) responses persisted in the absence of extracellular calcium, indicating that Ca2+ was released from intracellular stores. The source of calcium was distinct from [Ca2+](i)- activated (ruthenium red and ryanodine sensitive) or IP3-activated (thapsigargin-sensitive) Ca2+ stores and was not dependent on cGMP production because a cell permeant analog, 8-bromo-cGMP, did not increase basal [Ca2+](i). Glucose removal potentiated the NO-induced release of [Ca2+](i). In contrast, pretreatment with either the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone or cyclosporin A, a blocker of the mitochondrial permeability transition pore, prevented the [Ca2+](i) increase after NO. The rise in [Ca2+](i) during NO exposure was preceded by a decrease in mitochondrial membrane potential that was partly reversible during washout. Repeated applications of NMDA induced irreversible [Ca2+](i) responses in a subpopulation of striatal cells that were greatly reduced by the NOS inhibitor N-omega-nitro-L-arginine. Calcium transients were prolonged by conjoint application of NMDA and NO. We conclude that NMDA-evoked [Ca2+](i) transients are modulated by endogenous NO production, which leads to release of calcium from the mitochondrial pool. An NO-activated mitochondrial permeability transition pore may lead to cell death after overstimulation of NMDA receptors. |
| Document Type: Article |
| Language: English |
| Reprint Address: Horn, TFW (reprint author), Univ Magdeburg, Inst Med Neurobiol, Leipziger Str 44, D-39120 Magdeburg, Germany |
Addresses:
1. Univ Magdeburg, Inst Med Neurobiol, D-39120 Magdeburg, Germany
2. Univ Alberta, Dept Physiol, Edmonton, AB T6G 2M7 Canada
3. Univ Calgary, Neurosci Res Grp, Calgary, AB T2N 1N4 Canada |
| Publisher: FEDERATION AMER SOC EXP BIOL, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA |
| Subject Category: Biochemistry & Molecular Biology; Biology; Cell Biology |
| IDS Number: 614BN |
| ISSN: 0892-6638 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |