Premium
Nitric Oxide Disrupts Ca 2+ Homeostasis in Hippocampal Neurons
Author(s) -
Brorson James R.,
Sulit Reginaldo A.,
Zhang He
Publication year - 1997
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.1471-4159.1997.68010095.x
Subject(s) - nitric oxide , chemistry , peroxynitrite , depolarization , biophysics , neurotoxicity , homeostasis , nitric oxide synthase , hippocampal formation , biochemistry , oligomycin , endocrinology , biology , toxicity , superoxide , organic chemistry , enzyme , atpase
Nitric oxide has been recognized in recent years as an important mediator of neuronal toxicity, which in many cases involves alterations of the cytoplasmic Ca 2+ concentration ([Ca 2+ ] i ). In [Ca 2+ ] i fluorimetric experiments on cultured hippocampal neurons, the nitric oxide‐releasing agent S ‐nitrosocysteine produced a delayed rise in [Ca 2+ ] i over a 20‐min exposure, which was accompanied by a progressive slowing of the kinetics of recovery from depolarization‐induced [Ca 2+ ] 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 [Ca 2+ ] 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‐[Ca 2+ ] i fluorimetry experiments, S ‐nitrosocysteine had no effect on the resting [Ca 2+ ] i or on the recovery kinetics of [Ca 2+ ] i transients induced by direct depolarization. We conclude that prolonged exposure to nitric oxide disrupts [Ca 2+ ] i homeostasis in hippocampal neurons by impairing Ca 2+ removal from the cytoplasm, possibly as a result of ATP depletion. The resulting persistent alterations in [Ca 2+ ] i may contribute to the delayed neurotoxicity of nitric oxide.