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Journal of Neuroscience, Vol 14, 5613-5622, Copyright © 1994 by Society for Neuroscience
Pharmacological identification of two types of presynaptic voltage- dependent calcium channels at CA3-CA1 synapses of the hippocampus
LG Wu and P Saggau
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
The effects of voltage-dependent Ca channel (VDCC) antagonists on synaptic
transmission were investigated at CA3-CA1 synapses of guinea pig
hippocampal slices. After selectively loading presynaptic structures in
area CA1 with the calcium indicator fura-2, we simultaneously recorded a
presynaptic calcium transient ([Ca]t) and the corresponding field
excitatory postsynaptic potential (fEPSP) evoked by a single stimulus given
to the Schaffer collateral-commissural (SCC) pathway. Application of
nifedipine did not reduce either the [Ca]t of the fEPSP, suggesting that
nifedipine-sensitive Ca channels do not significantly contribute to evoked
synaptic transmission at low stimulation frequency. Application of
omega-conotoxin GVIA (omega-CgTX) or omega-agatoxin-IVA (omega-Aga-IVA)
dose-dependently blocked both the [Ca]t and the fEPSP. The time course of
the block of the [Ca]t was similar to that of the fEPSP. About 40% of the
total [Ca]t was omega- CgTX sensitive, and more than 20% was omega-Aga-IVA
sensitive. Combined application of these two blockers showed no overlap of
the omega-CgTX- sensitive with the omega-Aga-IVA-sensitive [Ca]t. These
results suggest that there are at least two types of presynaptic VDCCs at
CA3-CA1 synapses of the hippocampus: omega-CgTX-sensitive and
omega-Aga-IVA- sensitive Ca channels. Our results also suggest that these
two types of Ca channels are colocalized at a single presynaptic terminal.
During application of omega-CgTX or omega-Aga-IVA, the initial slope of the
fEPSP varied approximately as the fourth power of the amplitude of the
[Ca]t, suggesting that omega-CgTX-sensitive and omega-Aga-IVA-sensitive Ca
channels have about equal efficacy in triggering transmitter release. These
results in combination with similar findings at the squid giant synapse
suggest that the nonlinear relationship between transmitter release and the
Ca influx is well conserved from the molluscan to the mammalian nervous
system.
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