title: The use of invertebrate peptide toxins to establish Ca2+ channel identity of CA3-CA1 neurotransmission in rat hippocampal slices.
abstract: The 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.
authors.affiliation: Lilly Research Centre, Windlesham, Surrey, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Nooney
authors.forename: D
authors.initials: D
authors.lastname: Lodge
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018377:Neurotransmitter Agents; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D020866:omega-Conotoxin GVIA; D002118:Calcium