PHARMACOLOGICAL CHARACTERIZATION OF THE VOLTAGE-DEPENDENT CA2-NERVOUS-SYSTEM( CHANNELS PRESENT IN SYNAPTOSOMES FROM RAT AND CHICKEN CENTRAL)

The voltage-dependent calcium channels present in mammalian and chicke n brain synaptosomes were characterized pharmacologically using specif ic blockers of L-type channels (1,4-dihydropyridines), N-type channels (omega-conotoxin GVIA), and P-type channels [funnel web toxin (FTX) a nd omega-agatoxin IVA], K+-induced Ca2+ uptake by chicken synaptosomes was blocked by omega-conotoxin GVIA (IC50 = 250 nM). This toxin at 5 mu M did not block Ca2+ entry into rat frontal cortex synaptosomes. FT X and omega-agatoxin IVA blocked Ca2+ uptake by rat synaptosomes (IC50 = 0.17 mu l/ml and 40 nM, respectively). Likewise, in chicken synapto somes, FTX and omega-agatoxin IVA affected Ca2+ uptake. FTX (3 mu l/ml ) exerted a maximal inhibition of 40% with an IC50 similar to the one obtained in rat preparations, whereas with omega-agatoxin IVA saturati on was not reached even at 5 mu M. In chicken preparations, the combin ed effect of saturating concentrations of FTX(1 mu l/ml) and different concentrations of omega-conotoxin GVIA showed no additive effects. Ho wever, the effect of saturating concentrations of FTX and omega-conoto xin GVIA was never greater than the one observed with omega-conotoxin GVIA. We also found that 60% of the Ca2+ uptake by rat and chicken syn aptosomes was inhibited by omega-conotoxin MVIID (1 mu M), a toxin tha t has a high index of discrimination against N-type channels. Converse ly, nitrendipine (10 mu M) had no significant effect on Ca2+ uptake in either the rat or the chicken. In conclusion, Ca2+ uptake by rat syna ptosomes is potently inhibited by different P-type Ca2+ channel blocke rs, thus indicating that P-type channels are predominant in this prepa ration. In contrast, Ca2+ uptake by chicken synaptosomes is sensitive to omega-conotoxin GVIA, FTX, omega-agatoxin IVA, and omega-conotoxin MVIID. This suggests that a channel subtype with a mixed pharmacology is present in chicken synaptosomes.