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 Nand 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.
Presynaptic R-type calcium channels contribute to fast excitatory synaptic transmission in the rat hippocampus
PIETROBON, DANIELA;
2001
Abstract
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 Nand 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.
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