Presynaptic R-Type Calcium Channels Contribute to Fast Excitatory Synaptic Transmission in the Rat Hippocampus

Abstract

The possibility that R-type calcium channels contribute to fast glutamatergic transmission in the hippocampus has been assessed using low concentrations of NiCl(2) 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 NiCl(2) and SNX 482 were tested on large (composite) EPSCs evoked by mossy and associative-commissural fiber stimulation. NiCl(2) 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 NiCl(2) 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 NiCl(2) on R-type calcium channels. Together, these observations indicate that both NiCl(2) 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.

R-Type Calcium Channels Contribute to Afterdepolarization and Bursting in Hippocampal CA1 Pyramidal Neurons

“…The properties of the isolated current compare favorably with those reported for R-type calcium current Tsien, 1995, 1997). Previously reported functions for R-type current include the control of neurotransmitter release (Wu et al, 1998;Gasparini et al, 2001), the enhancement of presynaptic plasticity (Dietrich et al, 2003), and calcium entry into dendrites Magee and Johnston, 1995a,b;Magee et al, 1995;Isomura et al, 2002;Yasuda et al, 2003). Our results, demonstrating that R-type current is a critical component in generating the ADP and bursting, identify a novel role of this current in cellular excitability.…”

“…R-type calcium channels are also modulated by LTP-inducing stimuli, resulting in increased calcium entry into dendritic spines (Yasuda et al, 2003), and they play a role in apoptosis associated with juvenile myoclonic epilepsy (Suzuki et al, 2004). In other cell types, R-type current contributes to neurotransmitter release (Wu et al, 1998;Gasparini et al, 2001) and presynaptic plasticity (Dietrich et al, 2003). Our study is the first to identify R-type currents as an important A mixture of calcium channel antagonists (Mix) 10 M nimodipine with either 100 M -conotoxin GVIA and 100 nM -agatoxin IVA (n ϭ 7) or 10 M -conotoxin MVIIC (n ϭ 7) reduced the tail current.…”

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

“…Ca 2+ -imaging experiments recently suggested the presence of R-type Ca 2+ channels in a subset of hippocampal mossy fiber boutons [59]. It remains to be shown whether these findings can be confirmed in direct recordings and what role R-type Ca 2+ channels play in mossy fiber synaptic transmission [16,32].…”

Old proteins, developing roles: The regulation of calcium channels by synaptic proteins

“…24 The R-type channel also localizes presynaptically and may participate in neurotransmitter release, 32 although its contribution is smaller and varies with brain region. 33,34 With a few exceptions, it has been suggested that calcium channel isoforms are developmentally regulated with N-and R-type common in immature terminals, later favoring P/Q-type in maturity. 34,35 In the CNS, P/Q-type channels are often associated with excitatory synaptic transmission, whereas N-type channels tend to be involved in inhibitory neurotransmission.…”