Jm. Nooney et D. Lodge, THE USE OF INVERTEBRATE PEPTIDE TOXINS TO ESTABLISH CA2-CA1 NEUROTRANSMISSION IN RAT HIPPOCAMPAL SLICES( CHANNEL IDENTITY OF CA3), European journal of pharmacology, 306(1-3), 1996, pp. 41-50
The relative contribution(s) of different Ca2+ channel subtypes to syn
aptic transmission between Schaffer collaterals of hippocampal CA3 pyr
amidal cells and CA1 pyramidal cell dendrites has been assessed using
the synthetic invertebrate peptide toxins omega-conotoxin GVIA to bloc
k N-type Ca2+ channels, omega-agatoxin-IVA to block P-type Ca2+ channe
ls and omega-conotoxin MVIIC to block N-, P- and Q-type Ca2+ channels.
omega-Agatoxin-IVA, omega-conctoxin GVIA and omega-conotoxin MVIIC al
l produced dose-dependent inhibitions of the excitatory post-synaptic
field potential (fEPSP) recorded from the CA1 region of transverse hip
pocampal 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-ag
atoxin-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 b
y 85.7 +/- 15.3% (n = 3) at the end of 44 min application. Similar app
lications of 100 and 300 nM omega-conotoxin MVIIC reduced the fEPSP sl
ope 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) pro
duced no greater inhibition of the fEPSP than that observed with omega
-conotoxin GVIA alone, suggesting that the omega-agatoxin-IVA-sensitiv
e and omega-conotoxin MVIIC-sensitive component presents a pharmacolog
y 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, w
hich 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 transmi
ssion at Schaffer collateral-CAl synapses, they are not capable of sup
porting transmission when Q-type channels are blocked.