Back to Search
Start Over
Nitric oxide disrupts Ca2+ homeostasis in hippocampal neurons.
- Source :
-
Journal of neurochemistry [J Neurochem] 1997 Jan; Vol. 68 (1), pp. 95-105. - Publication Year :
- 1997
-
Abstract
- Nitric oxide has been recognized in recent years as an important mediator of neuronal toxicity, which in many cases involves alterations of the cytoplasmic Ca2+ concentration ([Ca2+]i). In [Ca2+]i fluorimetric experiments on cultured hippocampal neurons, the nitric oxide-releasing agent S-nitrosocysteine produced a delayed rise in [Ca2+]i over a 20-min exposure, which was accompanied by a progressive slowing of the kinetics of recovery from depolarization-induced [Ca2+]i transients. These effects were blocked by oxyhemoglobin and by superoxide dismutase, confirming nitric oxide as the responsible agent, and suggesting that they involved peroxynitrite formation. Similar alterations of [Ca2+]i homeostasis were produced by the mitochondrial ATP synthase inhibitor oligomycin, and when an ATP-regenerating system was supplied via the patch pipette in combined whole-cell patch-clamp-[Ca2+]i fluorimetry experiments, S-nitrosocysteine had no effect on the resting [Ca2+]i or on the recovery kinetics of [Ca2+]i transients induced by direct depolarization. We conclude that prolonged exposure to nitric oxide disrupts [Ca2+]i homeostasis in hippocampal neurons by impairing Ca2+ removal from the cytoplasm, possibly as a result of ATP depletion. The resulting persistent alterations in [Ca2+]i may contribute to the delayed neurotoxicity of nitric oxide.
- Subjects :
- Animals
Cysteine analogs & derivatives
Cysteine pharmacology
Cytoplasm metabolism
Fluorometry
Hippocampus cytology
Homeostasis drug effects
Osmolar Concentration
Patch-Clamp Techniques
Rats embryology
Rats, Inbred Strains
Calcium metabolism
Hippocampus metabolism
Homeostasis physiology
Neurons metabolism
Nitric Oxide physiology
S-Nitrosothiols
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3042
- Volume :
- 68
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 8978714
- Full Text :
- https://doi.org/10.1046/j.1471-4159.1997.68010095.x