N-type calcium channels play a dominant role in controlling synaptic t
ransmission in many peripheral neurons. Transmitter release from mamma
lian central nerve terminals, however, is relatively resistant to the
N channel antagonist omega-conotoxin GVIA. We studied the sensitivity
of glutamatergic synaptic transmission in rat hippocampal slices to om
ega-conotoxin and to omega-Aga-IVA, a P channel antagonist. Both toxin
s reduced the amplitude of excitatory postsynaptic potentials in CA1 p
yramidal neurons, but omega-Aga-IVA was the more rapid and efficacious
. These results were corroborated by biochemical studies measuring sub
second, calcium-dependent [H-3]glutamate release from hippocampal syna
ptosomes. Thus, at least two calcium channel types trigger glutamate r
elease from hippocampal neurons, but P-type plays a more prominent rol
e. Eliminating synaptic transmission in the CNS, therefore, may requir
e inhibiting more than a single calcium channel type.