Sertraline inhibits pre-synaptic Na+ channel-mediated responses in hippocampus-isolated nerve endings
Article first published online: 20 MAR 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 121, Issue 2, pages 197–205, April 2012
How to Cite
Aldana, B. I. and Sitges, M. (2012), Sertraline inhibits pre-synaptic Na+ channel-mediated responses in hippocampus-isolated nerve endings. Journal of Neurochemistry, 121: 197–205. doi: 10.1111/j.1471-4159.2012.07674.x
- Issue published online: 4 APR 2012
- Article first published online: 20 MAR 2012
- Accepted manuscript online: 30 JAN 2012 02:21PM EST
- Received October 6, 2011; revised manuscript received January 19 2012; accepted January 19, 2012.
- neurotransmitter release;
- sodium channels;
J. Neurochem. (2012) 121, 197–205.
In the present study, a possible sertraline action on cerebral pre-synaptic Na+ channels was investigated. For this purpose, the effect of sertraline on responses induced by the Na+ channel opener, veratridine, namely the increase in Na+ and in neurotransmitter release in hippocampus-isolated nerve endings was investigated. Results show that sertraline in the low μM range (1.5–25 μM) progressively inhibits the rise in Na+ and the release of pre-loaded [3H]Glu as well as the release of endogenous 5-HT, Glu and GABA (detected by HPLC) induced by veratridine depolarization either under external Ca2+-free conditions or in the presence of external Ca2+. In addition, under non-depolarized conditions, sertraline (25 μM) increased the external concentration of 5-HT at expense of its internal concentration, and unchanged the external and internal concentrations of the amino acid neurotransmitters and of the 5-HT main metabolite, 5-HIAA. This result is consistent with the sertraline inhibitory action of the serotonin transporter. However, sertraline is unlikely to inhibit pre-synaptic Na+ channels permeability by increasing external 5-HT. Because 5-HT in a wide concentration range (1–1000 μM) did not change the veratridine-induced increase in Na+. In summary, present findings demonstrate that besides the inhibition of 5-HT reuptake, sertraline is an effective inhibitor of pre-synaptic Na+ channels controlling neurotransmitter release.