Requirement of neural activity for the maintenance of dopaminergic neurons in rat midbrain slice cultures.
Chronic treatment of organotypic midbrain slice cultures with L-type Ca(2+) channel blocker nicardipine (3-10 microM) or verapamil (10 microM) for 18 days resulted in a drastic decrease in the number of dopaminergic neurons. A voltage-dependent Na(+) channel blocker tetrodotoxin (1 microM) was also effective in decreasing the number of dopaminergic neurons. Concurrent application of forskolin (20 microM) or dibutyryl cyclic AMP (1 mM) counteracted the effects of nicardipine and tetrodotoxin. These results suggest that spontaneous neuronal activity within midbrain slice cultures, causing Ca(2+) influx through L-type Ca(2+) channels that maintains intracellular cyclic AMP levels, is required for the maintenance of dopaminergic neurons.
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, 606-8501, Kyoto, Japan.
H
H
Katsuki
C
C
Takenaka
T
T
Kume
S
S
Kaneko
A
A
Akaike
D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D004298:Dopamine / Q000378:metabolism*; D008636:Mesencephalon / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D005576:Colforsin; D013779:Tetrodotoxin; D014700:Verapamil; D009529:Nicardipine; D004298:Dopamine