Inhibition of voltage-dependent calcium channels by o-conotoxin MVIIC (w-CTx-MVIIC) was studied in various types of rat neurons. When studied with 5 mM Ba*+ as charge carrier, w-CTx-MVIIC block of N-type calcium channels in sympathetic neurons was potent, with half-block at 18 nM. Block of N-type channels had a rapid onset (7 -1 set at 1 FM w-CTx-MVIIC) and quick reversibility (7 -30 set). The rate of block was proportional to toxin concentration, consistent with 1:l binding of toxin to

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... , with a rate constant (k") of -1 X IO6 M-' . set-'. Both potency and rate of block were reduced dramatically with increasing concentrations of extracellular Ba*+. o-CTx-MVIIC also blocked P-type calcium channels in cerebellar Purkinje neurons, but both development and reversal of block were far slower than for N-type channels. The rate of block was proportional to toxin concentration, with k", -1.5 x lo3 M-' * sect' at 5 mM Ba*+. From this value and an unblocking time constant of -200 min, a dissociation constant of -50 nM was estimated. Thus, block of P-type channels is potent but very slow. In hippocampal CA3 pyramidal neurons, o-CTx-MVIIC blocked -50% of the high-threshold calcium channel current; one component (-20%) was blocked with the rapid kinetics expected for N-type channels, whereas the other component was blocked slowly. The component blocked slowly was reduced but not eliminated by preexposure to 200 nM or 1 PM o-Aga-IVA.