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Pharmacological Characterization of the Voltage‐Dependent Ca 2+ Channels Present in Synaptosomes from Rat and Chicken Central Nervous System
Author(s) -
Maubecin Verónica Alvarez,
Sanchez Vivia.,
Rosato Siri Marcelo D.,
Cherksey Bruce D.,
Sugimori Mutzuyuki,
Llinás Rodolfo,
Uchitel Osvaldo D.
Publication year - 1995
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 - 10.1046/j.1471-4159.1995.64062544.x
Subject(s) - central nervous system , synaptosome , nervous system , chemistry , biophysics , neuroscience , characterization (materials science) , biology , materials science , nanotechnology
The voltage‐dependent calcium channels present in mammalian and chicken brain synaptosomes were characterized pharmacologically using specific blockers of L‐type channels (1,4‐dihydropyridines), N‐type channels (ω‐conotoxin GVIA), and P‐type channels [funnel web toxin (FTX) and ω‐agatoxin IVA]. K + ‐induced Ca 2+ uptake by chicken synaptosomes was blocked by ω‐conotoxin GVIA (IC 50 = 250 n M ). This toxin at 5 µ M did not block Ca 2+ entry into rat frontal cortex synaptosomes. FTX and ω‐agatoxin IVA blocked Ca 2+ uptake by rat synaptosomes (IC 50 = 0.17 µl/ml and 40 n M , respectively). Likewise, in chicken synaptosomes, FTX and ω‐agatoxin IVA affected Ca 2+ uptake. FTX (3 µl/ml) exerted a maximal inhibition of 40% with an IC 50 similar to the one obtained in rat preparations, whereas with ω‐agatoxin IVA saturation was not reached even at 5 µ M . In chicken preparations, the combined effect of saturating concentrations of FTX (1 µl/ml) and different concentrations of ω‐conotoxin GVIA showed no additive effects. However, the effect of saturating concentrations of FTX and ω‐conotoxin GVIA was never greater than the one observed with ω‐conotoxin GVIA. We also found that 60% of the Ca 2+ uptake by rat and chicken synaptosomes was inhibited by ω‐conotoxin MVIID (1 µ M ), a toxin that has a high index of discrimination against N‐type channels. Conversely, nitrendipine (10 µ M ) had no significant effect on Ca 2+ uptake in either the rat or the chicken. In conclusion, Ca 2+ uptake by rat synaptosomes is potently inhibited by different P‐type Ca 2+ channel blockers, thus indicating that P‐type channels are predominant in this preparation. In contrast, Ca 2+ uptake by chicken synaptosomes is sensitive to ω‐conotoxin GVIA, FTX, ω‐agatoxin IVA, and ω‐conotoxin MVIID. This suggests that a channel subtype with a mixed pharmacology is present in chicken synaptosomes.