Selective depression of low-release probability excitatory synapses by sodium channel blockers

Murali Prakriya, Steven Mennerick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

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 anti-glutamate 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.

Original languageEnglish (US)
Pages (from-to)671-682
Number of pages12
JournalNeuron
Volume26
Issue number3
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)

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