Rescue of mesencephalic dopaminergic neurons in culture by low-level stimulation of voltage-gated sodium channels

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Bénédicte Salthun-LassallePatrick P Michel

Abstract

We used a model system in which dopaminergic (DA) neurons from embryonic rat mesencephalon undergo spontaneous and selective degeneration as they develop in culture. Here, we show that DA cell loss can be prevented efficiently by low concentrations of the Na+ channel agonist veratridine. The survival promoting effect of veratridine was reproduced by, but independent of, glial cell line-derived neurotrophic factor. Neuroprotection by veratridine was exquisitely specific to DA neurons, short-lived after withdrawal, and abolished by tetrodotoxin, indicating that activation of voltage-gated Na+ channels was crucially involved. Calcium measurements showed that veratridine-induced Na+ influx was necessary to maintain intracellular Ca2+ within a neuroprotective range through the stimulation of low-voltage activated T-type calcium channels, a mechanism that was distinct from that elicited by high K+-evoked depolarization. Interestingly, increasing neuronal excitability by treatment with apamin, an inhibitor of Ca2+-activated K+ channels, or with ouabain, a blocker of the Na+/K+-ATPase pump, was also neuroprotective by a mechanism involving T-type calcium channel activation. These results support the idea that mesencephalic DA neurons d...Continue Reading

Citations

Sep 6, 2011·Nature Neuroscience·Daniel Alvarez-FischerAlain Prochiantz
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Apr 19, 2012·Human Molecular Genetics·Jack-Christophe CossecMarie-Claude Potier
Jul 21, 2009·Neuroreport·Peter J MorganMoritz J Frech
Apr 28, 2006·Science's STKE : Signal Transduction Knowledge Environment·Patrick P MichelEtienne Hirsch
Aug 22, 2007·Molecular and Cellular Biology·Hirochika KitagawaLeonard P Freedman
Feb 25, 2014·Pflügers Archiv : European journal of physiology·Benjamin J KopeckyJianxin Bao
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Apr 4, 2007·Journal of Neurochemistry·Patrick P MichelEtienne C Hirsch
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May 20, 2016·Neuron·Patrick P MichelStéphane Hunot

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