[Inhibitory effects of imipramine on intracellular Ca2+ mobilization in rat fronto-cortical cultured neurons]

We examined the effects of imipramine on cytosolic Ca2+ concentration ([Ca2+]i) in rat fronto-cortical cultured neurons exposed to various treatments (high K+, acetylcholine; ACh or noradrenaline; NA) using the Ca(2+)-sensitive dye fura-2. Imipramine inhibited high K(+)-induced [Ca2+]i increases with IC50 value of 71 microM, after washing the cells free of the drug, these effects were abolished. ACh and NA increased [Ca2+]i in a dose-dependent manner. Imipramine also inhibited ACh- and NA-induced [Ca2+]i increases with IC50 values of 3.7 and 4.1 microM, respectively. These results indicated that imipramine inhibited the high K(+)-induced [Ca2+]i increase by the blockade of voltage-dependent Ca2+ channels, and the ACh- and NA-induced ]Ca2+i increases by the blockade of muscarinic receptors and alpha 1-adrenoceptors, respectively. Moreover, imipramine abolished the [Ca2+]i oscillations, periodic fluctuations in [Ca2+]i were observed in a few cells only. Because [Ca2+]i oscillations were mediated by not only voltage-dependent Ca2+ channels, but also various receptors, it was likely that the inhibition of [Ca2+]i oscillations by imipramine was due to the blockade of voltage-dependent Ca2+ channels, muscarinic receptors or alpha 1-adrenoceptors.