ANTIDEPRESSANTS INHIBIT SPONTANEOUS OSCILLATIONS OF INTRACELLULAR CA2+ CONCENTRATION IN RAT CORTICAL CULTURED NEURONS

In rat cortical cultured neurons, spontaneous oscillations in the intracellular Ca" 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 muM. In addition, amitriptyline inhibited high K+- and glutamate-induced [Ca2+]i increases with IC50 values of 19 and 27 muM, respectively. Imipramine and mianserin also inhibited the high K+-induced [Ca2+]i increases with IC50 values of 45 and 24 muM, 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.