Presynaptic resurgent Na+ currents sculpt the action potential waveform and increase firing reliability at a CNS nerve terminal

Jun Hee Kim, Christopher Kushmerick, Henrique Von Gersdorff

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Axonal and nerve terminal action potentials often display a depolarizing after potential (DAP). However, the underlying mechanism that generates the DAP, and its impact on firing patterns, are poorly understood at axon terminals. Here, we find that at calyx of Held nerve terminals in the rat auditory brainstem the DAP is blocked by low doses of externally applied TTX or by the internal dialysis of low doses of lidocaine analog QX-314. The DAP is thus generated by a voltage-dependent Na+ conductance present after the action potential spike. Voltage-clamp recordings from the calyx terminal revealed the expression of a resurgent Na+ current (INaR), the amplitude of which increased during early postnatal development. The calyx of Held also expresses a persistent Na+ current (INaP), but measurements of calyx INaP together with computer modeling indicate that the fast deactivation time constant of INaP minimizes its contribution to the DAP. INaP is thus neither sufficient nor necessary to generate the calyx DAP, whereas INaR by itself can generate a prominent DAP. Dialysis of a small peptide fragment of the auxiliary β4 Na+ channel subunit into immature calyces (postnatal day 5- 6) induced an increase in INaR and a larger DAP amplitude, and enhanced the spike-firing precision and reliability of the calyx terminal. Our results thus suggest that an increase of INaR during postnatal synaptic maturation is a critical feature that promotes precise and resilient high-frequency firing.

Original languageEnglish (US)
Pages (from-to)15479-15490
Number of pages12
JournalJournal of Neuroscience
Volume30
Issue number46
DOIs
StatePublished - Nov 17 2010

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Action Potentials
Dialysis
Peptide Fragments
Presynaptic Terminals
Lidocaine
Brain Stem
QX-314

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Presynaptic resurgent Na+ currents sculpt the action potential waveform and increase firing reliability at a CNS nerve terminal. / Kim, Jun Hee; Kushmerick, Christopher; Von Gersdorff, Henrique.

In: Journal of Neuroscience, Vol. 30, No. 46, 17.11.2010, p. 15479-15490.

Research output: Contribution to journalArticle

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