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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 alpha 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 omega -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 alpha 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; omega -conotoxin-MVIIC; SNX 482


Copyright © 2001 Society for Neuroscience  0270-6474/01/21228715-07$05.00/0


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