Selective depression of low-release probability excitatory synapses by sodium channel blockers.
Sodium channels (NaChs) play a central role in action potential generation and are uniquely poised to influence the efficacy of transmitter release. We evaluated the effect of partial NaCh blockade on two aspects of synaptic efficacy First, we evaluated whether NaCh blockade accounts for the ability of certain drugs to selectively depress glutamate release. Second, we evaluated the contribution of NaChs to intraneuronal variability in glutamate release probability (p(r)). The antiglutamate drug riluzole nearly completely depresses glutamate excitatory postsynaptic currents (EPSCs) at concentrations that barely affect GABAergic inhibitory postsynaptic currents (IPSCs). NaCh inhibition explains the selective depression. Unlike other presynaptic depressants, partial NaCh blockade increases paired-pulse EPSC depression. This result is explained by selective depression of low-p(r) synapses. We conclude that local variations in the action potential contribute to p(r) variability among excitatory synapses.
Prakriya
M
M
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Mennerick
S
S
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019782:Riluzole