Presynaptic R-type calcium channels contribute to fast excitatory synaptic transmission in the rat hippocampus.
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.
Gasparini
S
S
Neuroscience Program and Istituto Nazionale Fisica della Materia Unit, International School for Advanced Studies, 34014 Trieste, Italy.
Kasyanov
A M
AM
Pietrobon
D
D
Voronin
L L
LL
Cherubini
E
E
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020908:Calcium Channels, R-Type / Q000187:drug effects / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D020908:Calcium Channels, R-Type; C115521:SNX 482; D013111:Spider Venoms; C022838:nickel chloride; D009532:Nickel