Proportions of Ca2+ channel subtypes in chick or rat P-2 fraction and NG108-15 cells using various Ca2+ blockers

The proportions of calcium (Ca2+) channel subtypes in chick or rat P-2 frac tion and NG 108-15 cells were investigated using selective L-, N-, P- and P /Q- type Ca2+ channel blockers. KCl-stimulated Ca-45(2+) uptake by chick Pt fraction was blocked by 40 similar to 50% using N-type Ca2+ channel blocke rs [omega-conotoxin GVIA, aminoglycoside antibiotics and dynorphin A(1-13)] , but was not inhibited by P- or P/Q-type blockers (omega-agatoxin IVA or o mega-conocoxin MVIIC). On the other hand, KCl-stimulated Ca-45(2+) uptake b y rat P-2 fraction was blocked by 30 similar to 40% using P- or P/Q-type Ca 2+ channel blockers, but was not inhibited by N-type Ca2+ channel blockers. The L-type Ca2+ channel blockers 1,4-dihydropyridines, diltiazem and verap amil, but not calciseptine (CaS), inhibited both KCl-stimulated Ca-45(2+) u ptake and veratridine-induced Na-22(+) uptake by chick or rat P-2 fraction with similar IC50 values. CaS did not have any effect on Ca-45(2+) uptake b y either chick or rat P-2 fraction. In NG108-15 cells, CaS, omega-agatoxin IVA and omega-conotoxin MVIIC, but not omega-conotoxin GVIA, inhibited KCl- stimulated Ca-45(2+) uptake by 30-40%. Various combinations of these Ca2+ c hannel blockers had no significant additional effects in chick or rat P-2 f raction or NG 108-15 cells. These findings suggest that KCl-stimulated Ca-4 5(2+) uptake by chick or rat P-2 fraction and NG 108-15 cells is a convenie nt and useful model for screening whether or not natural or synthetic subst ances have selective effects as L-, N-, P-, or P/Q- type Ca2+ channel antag onists or agonists.