D-600 blocks open Ca2+ channels more profoundly than closed ones.

The open channel blocking action of the Ca2+ antagonists, D-600 and Cd2+, was investigated in single neurons isolated by enzymatic treatment from dorsal root ganglia of frog. Using a 'concentration clamp' (jump) technique Ca2+ antagonists were applied to the preparation just before (less than 100 ms) or during a depolarizing step which induced the maximal peak amplitude of Ca2+ current (ICa). The inhibitory action of D-600 was more pronounced when applied during a depolarizing step than when applied just before a depolarizing step. In contrast, Cd2+ was equally inhibitory, whether applied before or during the depolarization. Thus, D-600 affects open channels more quickly or more profoundly than closed ones, while Cd2+ acts equally on both open and closed Ca2+ channels.