Effects of antidepressants on gamma-aminobutyric acid- and N-methyl-D-aspartate-induced intracellular Ca(2+) concentration increases in primary cultured rat cortical neurons.
We investigated the effects of antidepressants on the intracellular Ca2+ concentration ([Ca2+]i) increases induced by gamma-aminobutyric acid (GABA) or N-methyl-D-aspartate (NMDA) in primary cultured rat cortical neurons using fluorescence imaging. Acute treatment with imipramine inhibited GABA- and NMDA-induced increases in [Ca2+]i in a concentration-dependent manner. Doses of 30 microM clomipramine, desipramine, amoxapine and maprotiline also inhibited both the GABA- and NMDA-induced [Ca2+]i increases significantly. Both inhibitory effects of the five major antidepressants on the GABA- or the NMDA-induced [Ca2+]i increases were well-correlated. Imipramine could inhibit significantly high-K+-induced [Ca2+]i increases. Our previous study has already shown that the GABA-induced [Ca2+]i increase involves a similar pathway to high-K+-induced Ca2+ influx. In conclusion, imipramine and several other antidepressants have acute inhibitory effects on the GABA-, NMDA- and high-K+-induced [Ca2+]i increases, suggesting that these inhibitory effects are not related to specific receptors. One possibility is that these effects may be commonly mediated via part of the high-K+-induced [Ca2+]i pathway.
Takebayashi
M
M
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Hiroshima, Japan.
Kagaya
A
A
Inagaki
M
M
Kozuru
T
T
Jitsuiki
H
H
Kurata
K
K
Okamoto
Y
Y
Yamawaki
S
S
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000928:Antidepressive Agents; D015220:Calcium Channels; D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D011188:Potassium; D002118:Calcium