Dihydropyridine modulation of voltage-activated calcium channels in PC12 cells: effect of pertussis toxin pretreatment.
In this study, we report the effect of pertussis toxin pretreatment on dihydropyridine modulation of voltage-sensitive calcium channels in PC12 cells. The rise in intracellular calcium concentration caused by potassium depolarization is not affected significantly by pertussis toxin pretreatment. Nicardipine, a dihydropyridine derivative, added either before or after potassium-induced depolarization, reduces the resultant elevation in cytosolic calcium level both in control and in pertussis toxin-treated cells. The dihydropyridine agonist Bay K 8644, when added before potassium, is able to enhance the potassium-induced spike of cytosolic calcium levels, an effect significantly reduced by pertussis toxin pretreatment. Moreover, the addition of Bay K 8644 after potassium holds the intracellular calcium concentration at a cytosolic sustained level during the slow inactivating phase of depolarization. This effect of Bay K 8644 is inhibited by nicardipine. Pertussis toxin pretreatment slightly weakens the effect of Bay K 8644 when added after potassium-induced depolarization, whereas it significantly reduces the nicardipine inhibition of cytosolic calcium rise stimulated by potassium and Bay K 8644, but not by potassium alone. In conclusion, our findings suggest that a pertussis toxin-sensitive guanine nucleotide regulatory protein could be involved in the interaction between dihydropyridine derivatives and voltage-dependent calcium channels.
Schettini
G
G
Department of Pharmacology, II School of Medicine, University of Naples, Italy.
Meucci
O
O
Grimaldi
M
M
Florio
T
T
Landolfi
E
E
Scorziello
A
A
Ventra
C
C
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000310:Adrenal Gland Neoplasms / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D009529:Nicardipine / Q000494:pharmacology; D037342:Pertussis Toxin; D010673:Pheochromocytoma / Q000378:metabolism* / Q000473:pathology; D011188:Potassium / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010566:Virulence Factors, Bordetella; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D009529:Nicardipine; D037342:Pertussis Toxin; D011188:Potassium; D002118:Calcium