Antidepressants inhibit spontaneous oscillations of intracellular Ca2+ concentration in rat cortical cultured neurons.

In rat cortical cultured neurons, spontaneous oscillations in the intracellular Ca2+ concentration ([Ca2+]i) were observed by direct [Ca2+]i measurements using the fluorescent indicator fura-2. These [Ca2+]i responses were eliminated by the removal of extracellular Ca2-, L-type Ca2+ channel blockers or a glutamate receptor antagonist. Three antidepressants (amitriptyline, imipramine and mianserin) suppressed the [Ca2+]i oscillations in the range of 1-50 microM. In addition, amitriptyline inhibited high K(+)-and glutamate-induced [Ca2+]i increases with IC50 values of 19 and 27 microM, respectively. Imipramine and mianserin also inhibited the high K(+)-induced [Ca2+]i increases with IC50 values of 45 and 24 microM, respectively. These results suggest that blocking actions by the antidepressants on voltage-dependent Ca2+ influx and glutamate receptor-mediated Ca2+ influx may be involved in the suppression of the [Ca2+]i oscillations.