Sertraline inhibits pre-synaptic Na plus channel-mediated responses in hippocampus-isolated nerve endings

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 mu M range (1.525 mu M) 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 mu M) 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 (11000 mu M) 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.