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 language | English (US) |
|---|---|
| Pages (from-to) | 671-682 |
| Number of pages | 12 |
| Journal | Neuron |
| Volume | 26 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2000 |
Funding
The authors thank Joel Springer (University of Kentucky), members of the Zorumski Laboratory, Peter Lukasiewicz, Kel Yamada, Liu Lin Thio (Washington University), and Jack Waters (Stanford University) for valuable discussions and Ann Benz for preparation of hippocampal cultures. The authors are especially indebted to Chuck Zorumski for generous financial and intellectual support. This work was supported by a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (S. M.) and National Institutes of Health grant MH45493.
ASJC Scopus subject areas
- General Neuroscience