Presynaptic R-type calcium channels contribute to fast excitatory synaptictransmission in the rat hippocampus

The possibility that R-type calcium channels contribute to fast glutamaterg ic transmission in the hippocampus has been assessed using low concentratio ns of NiCl2 and the peptide toxin SNX 482, a selective antagonist of the po re-forming alpha (1E) subunit of R-type calcium channel. EPSPs or EPSCs wer e recorded in the whole-cell configuration of the patch-clamp technique mai nly from CA3 hippocampal neurons. Effects of both NiCl2 and SNX 482 were te sted 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 assoc iated with an increase in the number of response failures of minimal EPSPs- EPSCs, an enhancement of the paired-pulse facilitation ratios of both minim al and composite EPSCs, and a reduction of the inverse squared coefficient of variation (CV-2). The reduction of CV-2 was positively correlated with t he decrease in EPSC amplitude. The inhibitory effect of NiCl2 was occluded by SNX 482 but not by omega -conotoxin-MVIIC, a broad-spectrum antagonist t hought to interact with Nand P/Q-type calcium channels, supporting a specif ic action of low concentrations of NiCl2 on R-type calcium channels. Togeth er, these observations indicate that both NiCl2 and SNX 482 act at presynap tic sites and block R-type calcium channels with pharmacological properties similar to those encoded by the alpha (1E) gene. These channels are involv ed in fast glutamatergic transmission at hippocampal synapses.