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The Journal of Neuroscience, November 15, 2001, 21(22):8715-8721
Presynaptic R-Type Calcium Channels Contribute to Fast Excitatory
Synaptic Transmission in the Rat Hippocampus
Sonia
Gasparini1,
Alexander M.
Kasyanov1,
Daniela
Pietrobon2,
Leon L.
Voronin3, and
Enrico
Cherubini1
1 Neuroscience Program and Istituto Nazionale
Fisica della Materia Unit, International School for Advanced Studies,
34014 Trieste, Italy, 2 Department of Biomedical Sciences,
35121 Padova, Italy, and 3 Brain Research Institute,
Russian Academy of Medical Sciences, 103064 Moscow, Russia
The possibility that R-type calcium channels contribute to fast
glutamatergic transmission in the hippocampus has been assessed using
low concentrations of NiCl2 and the peptide toxin SNX 482, a selective antagonist of the pore-forming 1E subunit of
R-type calcium channel. EPSPs or EPSCs were recorded in the
whole-cell configuration of the patch-clamp technique mainly from CA3
hippocampal neurons. Effects of both NiCl2 and SNX 482 were
tested on large (composite) EPSCs evoked by mossy and
associative-commissural fiber stimulation. NiCl2 effects
were also tested on minimal EPSPs-EPSCs. Both substances reduced the
amplitude of EPSPs-EPSCs. This effect was associated with an increase
in the number of response failures of minimal EPSPs-EPSCs, an
enhancement of the paired-pulse facilitation ratios of both
minimal and composite EPSCs, and a reduction of the inverse squared
coefficient of variation (CV 2). The reduction of
CV 2 was positively correlated with the decrease in
EPSC amplitude. The inhibitory effect of NiCl2 was occluded
by SNX 482 but not by -conotoxin-MVIIC, a broad-spectrum antagonist
thought to interact with N- and P/Q-type calcium channels, supporting a
specific action of low concentrations of NiCl2 on R-type
calcium channels. Together, these observations indicate that both
NiCl2 and SNX 482 act at presynaptic sites and block R-type
calcium channels with pharmacological properties similar to those
encoded by the 1E gene. These channels are involved in
fast glutamatergic transmission at hippocampal synapses.
Key words:
hippocampus; mossy fibers; associative-commissural
fibers; single-fiber EPSPs; single-fiber EPSCs; composite EPSC; -conotoxin-MVIIC; SNX 482
Copyright © 2001 Society for Neuroscience 0270-6474/01/21228715-07$05.00/0
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