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Dihydropyridine Modulation of Voltage‐Activated Calcium Channels in PC12 Cells: Effect of Pertussis Toxin Pretreatment
Author(s) -
Schettini G.,
Meucci O.,
Grimaldi M.,
Florio T.,
Landolfi E.,
Scorziello A.,
Ventra C.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb01995.x
Subject(s) - nicardipine , dihydropyridine , pertussis toxin , calcium , depolarization , chemistry , potassium , biophysics , potassium channel , endocrinology , medicine , pharmacology , biochemistry , biology , g protein , receptor , organic chemistry
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.