Block of Multiple Presynaptic Calcium Channel Types by _-Conotoxin-MVIIC at Hippocampal CA3 to CA1 Synapses. WU, L.G., and P. Saggau. Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
APStracts 2:0047N, 1995.
SUMMARY AND CONCLUSIONS
1. The effect of the voltage-dependent Ca channel (VDCC) antagonist _- conotoxin-MVIIC (_-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. _-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 _-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 _-CTx-MVIIC inhibits the fEPSP by blocking presynaptic Ca channels at hippocampal CA3 to CA1 synapses. 3. Sequential application of high concentrations of _-CTx-MVIIC (10 [mu]M) and other VDCC blockers including _-conotoxin-GVIA (_-CTx-GVIA, 1 [mu]M) and _-agatoxin-IVA (_- Aga-IVA, 1 [mu]M) showed that _-CTx-MVIIC significantly occludes the effects of _-CTx-GVIA and _-Aga-IVA. Combined application of _-CTx-GVIA (1 [mu]M) and _-Aga- IVA (1 [mu]M) largely but not completely occluded the effect of _-CTx-MVIIC. These results suggest that _-CTx-MVIIC inhibits multiple types of presynaptic Ca channels, a large fraction of which are the _-CTx- GVIA_ or _-Aga- IVA_sensitive channels and a small portion of which are channels insensitive to high concentrations of _-CTx-GVIA and _-Aga-IVA. 4. Sequential or combined application of the above three toxins at high concentrations showed that _23_29% of the presynaptic [Ca] t is insensitive to these three toxins. 5. The presynaptic [Ca] t at CA3 to CA1 synapses was found to have at least four pharmacologically distinct components (expressed as mean): 1 ) _-CTx- GVIA sensitive (39%); 2 ) _-Aga-IVA sensitive (25%), the majority of which is also sensitive to _-CTx-MVIIC; 3 ) _-CTx-GVIA and _-Aga- IVA resistant (up to 1 [mu]M) but _-CTx-MVIIC sensitive (11%); and 4 ) _-CTx- GVIA, _-Aga-IVA, and _- CTx-MVIIC resistant (27%). On the basis of this pharmacological evidence, a functional classification of presynaptic Ca channel types including N, Q, and R type is discussed. These Ca channel types trigger transmitter release with a similar efficacy, suggesting that they are randomly distributed around transmitter release sites. 

Received 1 August 1994; accepted in final form 18 January 1995.
APS Manuscript Number J477-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  3 April 1995.