Presynaptic Na+ channels: Locus, development, and recovery from inactivation at a high-fidelity synapse

Ricardo M. Leão, Christopher Kushmerick, Raphael Pinaud, Robert Renden, Geng Lin Li, Holger Taschenberger, George Spirou, S. Rock Levinson, Henrique Von Gersdorff

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


Na+ channel recovery from inactivation limits the maximal rate of neuronal firing. However, the properties of presynaptic Na+ channels are not well established because of the small size of most CNS boutons. Here we study the Na+ currents of the rat calyx of Held terminal and compare them with those of postsynaptic cells. We find that presynaptic Na + currents recover from inactivation with a fast, single-exponential time constant (24°C, τ of 1.4-1.8 τ 35°C, τ of 0.5 ms), and their inactivation rate accelerates twofold during development, which may contribute to the shortening of the action potential as the terminal matures. In contrast, recordings from postsynaptic cells in brainstem slices, and acutely dissociated, reveal that their Na+ currents recover from inactivation with a double-exponential time course (τfast of 1.2-1.6 ms; τslow of 80-125 ms; 24°C). Surprisingly, confocal immunofluorescence revealed that Na+ channels are mostly absent from the calyx terminal but are instead highly concentrated in an unusually long (≈=20-40 μm) unmyelinated axonal heminode. Outside-out patch recordings confirmed this segregation. Expression of Nav1.6 α-subunit increased during development, whereas the Nav1.2 α-subunit was not present. Serial EM reconstructions also revealed a long pre-calyx heminode, and biophysical modeling showed that exclusion of Na+ channels from the calyx terminal produces an action potential waveform with a shorter half-width. We propose that the high density and polarized locus of Na + channels on a long heminode are critical design features that allow the mature calyx of Held terminal to fire reliably at frequencies near 1 kHz.

Original languageEnglish (US)
Pages (from-to)3724-3738
Number of pages15
JournalJournal of Neuroscience
Issue number14
StatePublished - Apr 6 2005


  • Action potential
  • Auditory
  • Calyx of Held
  • Heminode
  • High-frequency firing
  • Nodes of Ranvier
  • Presynaptic terminal
  • Sodium

ASJC Scopus subject areas

  • Neuroscience(all)


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