Role of voltage-sensitive calcium channels in mitogenic stimulation of neuroblasts.
The present study examines the role of Ca2+ in the regulation of sympathetic neuroblast mitosis. Employing a fully defined neuroblast culture system, we previously found that insulin growth factors (IGFs), depolarization and vasoactive intestinal peptide (VIP) regulated precursor mitosis. We now report that Ca2+ entry via voltage-sensitive channels was required for depolarization-stimulated mitogenesis. Ca2+ channel blockade with nitrendipine completely inhibited the increase in [3H]thymidine incorporation elicited by depolarizing stimuli including 30 mM KCl and the Na+ channel agonist veratridine. However, Ca2+ channel activity was not involved in the stimulation of DNA synthesis by IGFs or VIP. Thus, neuroblast mitosis may be regulated by multiple intracellular as well as extracellular signals.
Pincus
D W
DW
Department of Neurology, Cornell University Medical College, New York, NY 10021.
DiCicco-Bloom
E
E
Black
I B
IB
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009568:Nitrendipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007328:Insulin; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D011189:Potassium Chloride; D014701:Veratridine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D013936:Thymidine