Inhibitory effect of imipramine on depolarization-induced increases in intracellular Ca2+ of rat cortical neurons.
We examined the effects of imipramine on the increase in intracellular Ca2+ concentration ([Ca2+]i) induced by elevated K+ in cultured neurons of rat cortex. Imipramine (100 nM-200 microM) produced a concentration-dependent inhibition of [Ca2+]i increases induced by 25 mM K+ with an IC50 value of 32 microM. Imipramine had no effect on resting [Ca2+]i levels. When the cells were incubated with imipramine in the presence of a voltage-sensitive Ca2+ channel (VSCC) blocker, either nicardipine (10 microM), verapamil (10 microM), or omega-conotoxin GVIA (1 microM), the combinations of imipramine and each blocker resulted in an additive inhibition of 25 mM K(+)-induced [Ca2+]i increases. The IC50 values were 44, 29 and 24 microM, respectively, which were similar to those found when incubating the cells with imipramine alone. The presence or the absence of imipramine (30 microM) in an incubation with Bay K 8644 (100 nM), a VSCC agonist, showed similar potentiation of the [Ca2+]i increases induced by 15 mM K+ (66 and 52%, respectively). On the other hand, when the cells were incubated with imipramine in the presence of Ni2+ (300 microM) or La3+ (0.3 microM), inorganic Ca(2+)-channel blockers, the IC50 values of inhibition of 25 mM K(+)-induced [Ca2+]i increases were much lower than with imipramine alone (3.2 and 16 microM, respectively). However, incubations with Ni2+ combined with nicardipine or verapamil resulted in an additive inhibition of 25 mM K(+)-induced [Ca2+]i increases.(ABSTRACT TRUNCATED AT 250 WORDS)
Shimizu
M
M
Department of Psychiatry and Neuroscience, Institute of Clinical Research, Kure National Hospital, Japan.
Nishida
A
A
Fukuda
H
H
Saito
H
H
Yamawaki
S
S
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004563:Electrochemistry; D007099:Imipramine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010566:Virulence Factors, Bordetella; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007099:Imipramine; D011188:Potassium; D002118:Calcium