Sodium currents in medullary neurons isolated from the pre-Bötzinger complex region

Krzysztof Ptak, Greer G. Zummo, George F. Alheid, Tatiana Tkatch, D. James Surmeier, Donald R. McCrimmon*

*Corresponding author for this work

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

The pre-Bötzinger complex (preBötC) in the ventrolateral medulla contains interneurons important for respiratory rhythm generation. Voltage-dependent sodium channels mediate transient current (INaT), underlying action potentials, and persistent current (INaP), contributing to repetitive firing, pacemaker properties, and the amplification of synaptic inputs. Voltage-clamp studies of the biophysical properties of these sodium currents were conducted on acutely dissociated preBötC region neurons. Reverse transcription-PCR demonstrated the presence of mRNA for Nav1.1, Nav1.2, and Nav1.6 α-subunits in individual neurons. A TTX-sensitive INaP was evoked in all tested neurons by ramp depolarization from -80 to 0 mV. Including a constant in the Boltzmann equation for inactivation by estimating the steady-state fraction of Na+ channels available for inactivation allowed prediction of a window current that did not decay to 0 at voltages positive to -20 mV and closely matched the measured INaP. Riluzole (3 μM), a putative INaP antagonist, reduced both I NaP and INaT and produced a hyperpolarizing shift in the voltage dependence of steady-state inactivation. The latter decreased the predicted window current by an amount equivalent to the decrease in I NaP. Riluzole also decreased the inactivation time constant at potentials in which the peak window/persistent currents are generated. Together, these findings imply that INap and INaT arise from the same channels and that a simple modification of the Hodgkin-Huxley model can satisfactorily account for both currents. In the rostral ventral respiratory group (immediately caudal to preBötC), INaP was also detected, but peak conductance, current density, and input resistance were smaller than in preBötC region cells.

Original languageEnglish (US)
Pages (from-to)5159-5170
Number of pages12
JournalJournal of Neuroscience
Volume25
Issue number21
DOIs
StatePublished - May 25 2005

Keywords

  • Central pattern generator
  • Pacemaker
  • Persistent current
  • Pre-Bötzinger
  • Respiration
  • Riluzole
  • Sodium channels

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Sodium currents in medullary neurons isolated from the pre-Bötzinger complex region'. Together they form a unique fingerprint.

  • Cite this