Widespread distribution of dihydropyridine-sensitive calcium channels in the central nervous system.
We have used microspectrofluorimetry and the Ca2+-sensitive dye fura-2 to analyze the effects of dihydropyridine drugs on the voltage-sensitive influx of Ca2+ into central nervous system neurons grown in primary culture. Depolarization, induced by raising [K+]o, produced a rapid increase in [Ca2+]i measured in single neurons from the cortex, hippocampus, striatum, septum, and cerebellum. These increases were slightly attenuated when external Na+ was replaced by choline+ and were absent in Ca2+-free (1 mM EGTA) media. The depolarization-induced uptake of Ca2+ by neurons from all regions of the brain was enhanced by the dihydropyridine agonist BAY K8644 (1 microM). The dihydropryidine antagonist nitrendipine (1 microM) inhibited calcium influx into hippocampal and striatal neurons by 79% and 31%, respectively, indicating that different routes of voltage-dependent calcium influx predominate in neurons from different brain regions. The results establish the widespread distribution of functional dihydropyridine-sensitive Ca2+ channels in the central nervous system.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004095:Dihydropyridines; D006624:Hippocampus / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009928:Organ Specificity; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D004095:Dihydropyridines; D007473:Ion Channels; D011725:Pyridines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D002118:Calcium