Block of multiple presynaptic calcium channel types by omega-conotoxin-MVIIC at hippocampal CA3 to CA1 synapses.

1. The effect of the voltage-dependent Ca channel (VDCC) antagonist omega-conotoxin-MVIIC (omega-CTx-MVIIC) on the presynaptic Ca influx and synaptic transmission was studied in area CA1 of guinea pig hippocampus. The presynaptic Ca transient ([Ca]t) and the field excitatory postsynaptic potential (fEPSP) evoked by a single electrical stimulus were simultaneously recorded at CA3 to CA1 synapses. 2. omega-CTx-MVIIC dose dependently blocked the fEPSP and the presynaptic [Ca]t without affecting the presynaptic fiber volley and the presynaptic resting Ca level. During application of omega-CTx-MVIIC, the decrease of both the fEPSP and the presynaptic [Ca]t had a similar time course, and the initial slope of the fEPSP is proportional to about the fourth power of the amplitude of the presynaptic [Ca]t. These results strongly suggest that omega-CTx-MVIIC inhibits the fEPSP by blocking presynaptic Ca channels at hippocampal CA3 to CA1 synapses. 3. Sequential application of high concentrations of omega-CTx-MVIIC (10 microM) and other VDCC blockers including omega-conotoxin-GVIA (omega-CTx-GVIA, 1 microM) and omega-agatoxin-IVA (omega-Aga-IVA, 1 microM) showed that omega-CTx-MVIIC significantly occludes the effects of omega-CTx-GVIA and omega-Aga-IVA. Combined application of omega-CTx-GVIA (1 microM) and omega-Aga-IVA (1 microM) largely but not completely occluded the effect of omega-CTx-MVIIC.(ABSTRACT TRUNCATED AT 250 WORDS)