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Keywords:

  • 5-HT;
  • GABA;
  • Glu;
  • neurotransmitter release;
  • sodium channels;
  • veratridine

J. Neurochem. (2012) 121, 197–205.

Abstract

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.