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.
Shimizu
M
M
Department of Psychiatry and Neuroscience, Kure National Hospital, Japan.
Nishida
A
A
Yamawaki
S
S
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008803:Mianserin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D000928:Antidepressive Agents; D000639:Amitriptyline; D008803:Mianserin; D007099:Imipramine; D002118:Calcium