• J M Nooney and D Lodge.
• Lilly Research Centre, Windlesham, Surrey, UK.
• Eur. J. Pharmacol. 1996 Jun 13; 306 (1-3): 41-50.

AbstractThe relative contribution(s) of different Ca2+ channel subtypes to synaptic transmission between Schaffer collaterals of hippocampal CA3 pyramidal cells and CA1 pyramidal cell dendrites has been assessed using the synthetic invertebrate peptide toxins omega-conotoxin GVIA to block N-type Ca2+ channels, omega-agatoxin-IVA to block P-type Ca2+ channels and omega-conotoxin MVIIC to block N-, P- and Q-type Ca2+ channels. Omega-Agatoxin-IVA, omega-conotoxin GVIA and omega-conotoxin MVIIC all produced dose-dependent inhibitions of the excitatory post-synaptic field potential (fEPSP) recorded from the CA1 region of transverse hippocampal slices. Application of 300 nM omega-conotoxin GVIA generally produced no further inhibition to that observed with 100 nM, resulting in a maximal 50% inhibition of the fEPSP. By contrast, 30 nM omega-agatoxin-IVA reduced the fEPSP slope by only 4.6 +/- 11.1% (mean +/- S.D., n = 3), suggesting the lack of involvement of classical P-type Ca2+ channels, whereas 300 nM omega-agatoxin-IVA reduced the fEPSP slope by 85.7 +/- 15.3% (n = 3) at the end of 44 min application. Similar applications of 100 and 300 nM sigma-conotoxin MVIIC reduced the fEPSP slope by 30.9 +/- 6.6% and 79.7 +/- 5.7% respectively. Application of 30 nM omega-agatoxin-IVA together with omega-conotoxin GVIA (300 nM) produced no greater inhibition of the fEPSP than that observed with omega-conotoxin GVIA alone, suggesting that the omega-agatoxin-IVA-sensitive and omega-conotoxin MVIIC-sensitive component presents a pharmacology similar to the reported Q-type Ca2+ channel. The inhibition produced by omega-conotoxin GVIA and omega-conotoxin MVIIC showed no recovery with prolonged washing (1-2 h) whereas that produced by omega-agatoxin-IVA was slowly reversible. The observation that omega-agatoxin-IVA, which does not effect N-type Ca2+ channels (Mintz et al. (1992a) Neuron 9, 85), is capable of completely suppressing the fEPSP suggests that, whilst N-type Ca2+ channels may contribute to normal synaptic transmission at Schaffer collateral-CA1 synapses, they are not capable of supporting transmission when Q-type channels are blocked.

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