Pharmacological identification of two types of presynaptic voltage-dependent calcium channels at CA3-CA1 synapses of the hippocampus
Abstract
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…
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