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Brevetoxin activation of voltage-gated sodium channels regulates Ca2+ dynamics and ERK1/2 phosphorylation in murine neocortical neurons
- Source :
- Journal of Neurochemistry. 89:739-749
- Publication Year :
- 2004
- Publisher :
- Wiley, 2004.
-
Abstract
- Voltage-gated sodium channels (VGSC) are involved in the generation of action potentials in neurons. Brevetoxins (PbTx) are potent allosteric enhancers of VGSC function and are associated with the periodic 'red tide' blooms. Using PbTx-2 as a probe, we have characterized the effects of activation of VGSC on Ca(2+) dynamics and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling in neocortical neurons. Neocortical neurons exhibit synchronized spontaneous Ca(2+) oscillations, which are mediated by glutamatergic signaling. PbTx-2 (100 nm) increased the amplitude and reduced the frequency of basal Ca(2+) oscillations. This modulatory effect on Ca(2+) oscillations produced a sustained rise in ERK1/2 activation. At 300 nm, PbTx-2 disrupted oscillatory activity leading to a sustained increase in intracellular Ca(2+) ([Ca(2+)](i)) and induced a biphasic, activation followed by dephosphorylation, regulation of ERK1/2. PbTx-2-induced ERK1/2 activation was Ca(2+) dependent and was mediated by Ca(2+) entry through manifold routes. PbTx-2 treatment also increased cAMP responsive element binding protein (CREB) phosphorylation and increased gene expression of brain-derived neurotrophic factor (BDNF). These findings indicate that brevetoxins, by influencing the activation of key signaling proteins, can alter physiologic events involved in survival in neocortical neurons, as well as forms of synaptic plasticity associated with development and learning.
- Subjects :
- Neurotoxins
Allosteric regulation
Glutamic Acid
Neocortex
Biology
Biochemistry
Article
Sodium Channels
Mice
Cellular and Molecular Neuroscience
Brevetoxin
medicine
Animals
Neurotoxin
Calcium Signaling
Enzyme Inhibitors
Phosphorylation
Cyclic AMP Response Element-Binding Protein
Cells, Cultured
Calcium signaling
Mitogen-Activated Protein Kinase 1
Neurons
Mitogen-Activated Protein Kinase 3
Brain-Derived Neurotrophic Factor
Sodium channel
Oxocins
Enzymes
medicine.anatomical_structure
Biophysics
Calcium
Marine Toxins
Neuron
Mitogen-Activated Protein Kinases
Excitatory Amino Acid Antagonists
Ion Channel Gating
Neuroscience
Marine toxin
Subjects
Details
- ISSN :
- 14714159 and 00223042
- Volume :
- 89
- Database :
- OpenAIRE
- Journal :
- Journal of Neurochemistry
- Accession number :
- edsair.doi.dedup.....83ac8351dae960ac9f7703526cf21f8e