Biomedical subjects

John M Sarvey

Publications and source records attributed to John M Sarvey.

3 recordsLinked to original sources

PubMed2004

The mitochondrial toxin, 3-nitropropionic acid, induces extracellular Zn2+ accumulation in rat hippocampus slices.

3-nitropropionic acid (3-NPA), a suicide inhibitor of succinate dehydrogenase (SDH; complex II), has been used to provide useful experimental models of Huntington's disease (HD) and "chemical hypoxia" in rodents. The trace ion Zn2+ has been shown to cause neurodegeneration. Employing real-time Newport Green fluorescence imaging of extracellular Zn2+, we found that 3-NPA (10-100 microM) caused a concentration-dependent increase in the concentration of extracellular Zn2+ ([Zn2+]o) in acute rat hippocampus slices. This increase in [Zn2+]o was abolished by 10 mM CaEDTA. The increase of [Zn2+]o was also accompanied by a rapid increase of cytoplasmic-free Zn2+ concentration ([Zn2+]i). The induction of Zn2+ release by 3-MPA in hippocampus slices points to a potential mechanism by which 3-NPA might induce neurodegeneration.

Animals↗

PubMed2003

Do we need zinc to think?

Chelatable Zn(2+), which is found in the synaptic vesicles of certain glutamatergic neurons in several regions of the forebrain, is released during neuronal activity. Zn(2+) exhibits numerous effects on ligand-gated and voltage-dependent ion channels, and released Zn(2+) is therefore likely able to modulate synaptic transmission. The physiologically relevant actions of Zn(2+), however, have remained unclear. Recent research exploiting improved Zn(2+)-sensitive optical probes has suggested some intriguing effects for synaptically released Zn(2+), including heterosynaptic regulation of N-methyl-D-aspartate (NMDA) receptor function, and a novel role as a trans-synaptic second messenger that may enter postsynaptic neurons to modulate various signal transduction pathways.

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PubMed2003

Modulation of epileptiform burst frequency by the metabotropic glutamate receptor subtype mGluR3.

Spontaneous epileptiform burst activity occurs in acute hippocampal slice dentate granule cells perfused with 10mM potassium and 0.5mM calcium [J. Neurophys. 68 (1992) 2016]. We report that activation of the group II metabotropic glutamate receptor subtype 3 (mGluR3) induces an increase in spontaneous burst duration, whereas inhibition of mGluR3 reversibly reduces spontaneous burst frequency. Neither activation, nor inhibition, of group II mGluR had any effects on spontaneous negative dc shifts, or the number of spikes per burst, as compared to control. We conclude that mGluR3 can modulate high potassium, low calcium-induced spontaneous epileptiform burst activity in acute rat hippocampal slice dentate granule cells.

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