Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons

R. I. Herzog, Theodore Cummins, S. G. Waxman

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

Small dorsal root ganglion (DRG) neurons, which include nociceptors, express multiple voltage-gated sodium currents. In addition to a classical fast inactivating tetrodotoxin-sensitive (TTX-S) sodium current, many of these cells express a TTX-resistant (TTX-R) sodium current that activates near -70 mV and is persistent at negative potentials. To investigate the possible contributions of this TTX-R persistent (TTX-RP) current to neuronal excitability, we carried out computer simulations using the Neuron program with TTX-S and -RP currents, fit by the Hodgkin-Huxley model, that closely matched the currents recorded from small DRG neurons. In contrast to fast TTX-S current, which was well fit using a m3h model, the persistent TTX-R current was not well fit by an m3h model and was better fit using an mh model. The persistent TTX-R current had a strong influence on resting potential, shifting it from -70 to -49.1 mV. Inclusion of an ultra-slow inactivation gate in the persistent current model reduced the potential shift only slightly, to -56.6 mV. The persistent TTX-R current also enhanced the response to depolarizing inputs that were subthreshold for spike electrogenesis. In addition, the presence of persistent TTX-R current predisposed the cell to anode break excitation. These results suggest that, while the persistent TTX-R current is not a major contributor to the rapid depolarizing phase of the action potential, it contributes to setting the electrogenic properties of small DRG neurons by modulating their resting potentials and response to subthreshold stimuli.

Original languageEnglish (US)
Pages (from-to)1351-1364
Number of pages14
JournalJournal of Neurophysiology
Volume86
Issue number3
StatePublished - 2001
Externally publishedYes

Fingerprint

Sensory Receptor Cells
Membrane Potentials
Tetrodotoxin
Spinal Ganglia
Neurons
Sodium
Nociceptors
Computer Simulation
Action Potentials
Electrodes

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons. / Herzog, R. I.; Cummins, Theodore; Waxman, S. G.

In: Journal of Neurophysiology, Vol. 86, No. 3, 2001, p. 1351-1364.

Research output: Contribution to journalArticle

@article{44927f73add4403f9d7c300e8caa23aa,
title = "Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons",
abstract = "Small dorsal root ganglion (DRG) neurons, which include nociceptors, express multiple voltage-gated sodium currents. In addition to a classical fast inactivating tetrodotoxin-sensitive (TTX-S) sodium current, many of these cells express a TTX-resistant (TTX-R) sodium current that activates near -70 mV and is persistent at negative potentials. To investigate the possible contributions of this TTX-R persistent (TTX-RP) current to neuronal excitability, we carried out computer simulations using the Neuron program with TTX-S and -RP currents, fit by the Hodgkin-Huxley model, that closely matched the currents recorded from small DRG neurons. In contrast to fast TTX-S current, which was well fit using a m3h model, the persistent TTX-R current was not well fit by an m3h model and was better fit using an mh model. The persistent TTX-R current had a strong influence on resting potential, shifting it from -70 to -49.1 mV. Inclusion of an ultra-slow inactivation gate in the persistent current model reduced the potential shift only slightly, to -56.6 mV. The persistent TTX-R current also enhanced the response to depolarizing inputs that were subthreshold for spike electrogenesis. In addition, the presence of persistent TTX-R current predisposed the cell to anode break excitation. These results suggest that, while the persistent TTX-R current is not a major contributor to the rapid depolarizing phase of the action potential, it contributes to setting the electrogenic properties of small DRG neurons by modulating their resting potentials and response to subthreshold stimuli.",
author = "Herzog, {R. I.} and Theodore Cummins and Waxman, {S. G.}",
year = "2001",
language = "English (US)",
volume = "86",
pages = "1351--1364",
journal = "Journal of Neurophysiology",
issn = "0022-3077",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons

AU - Herzog, R. I.

AU - Cummins, Theodore

AU - Waxman, S. G.

PY - 2001

Y1 - 2001

N2 - Small dorsal root ganglion (DRG) neurons, which include nociceptors, express multiple voltage-gated sodium currents. In addition to a classical fast inactivating tetrodotoxin-sensitive (TTX-S) sodium current, many of these cells express a TTX-resistant (TTX-R) sodium current that activates near -70 mV and is persistent at negative potentials. To investigate the possible contributions of this TTX-R persistent (TTX-RP) current to neuronal excitability, we carried out computer simulations using the Neuron program with TTX-S and -RP currents, fit by the Hodgkin-Huxley model, that closely matched the currents recorded from small DRG neurons. In contrast to fast TTX-S current, which was well fit using a m3h model, the persistent TTX-R current was not well fit by an m3h model and was better fit using an mh model. The persistent TTX-R current had a strong influence on resting potential, shifting it from -70 to -49.1 mV. Inclusion of an ultra-slow inactivation gate in the persistent current model reduced the potential shift only slightly, to -56.6 mV. The persistent TTX-R current also enhanced the response to depolarizing inputs that were subthreshold for spike electrogenesis. In addition, the presence of persistent TTX-R current predisposed the cell to anode break excitation. These results suggest that, while the persistent TTX-R current is not a major contributor to the rapid depolarizing phase of the action potential, it contributes to setting the electrogenic properties of small DRG neurons by modulating their resting potentials and response to subthreshold stimuli.

AB - Small dorsal root ganglion (DRG) neurons, which include nociceptors, express multiple voltage-gated sodium currents. In addition to a classical fast inactivating tetrodotoxin-sensitive (TTX-S) sodium current, many of these cells express a TTX-resistant (TTX-R) sodium current that activates near -70 mV and is persistent at negative potentials. To investigate the possible contributions of this TTX-R persistent (TTX-RP) current to neuronal excitability, we carried out computer simulations using the Neuron program with TTX-S and -RP currents, fit by the Hodgkin-Huxley model, that closely matched the currents recorded from small DRG neurons. In contrast to fast TTX-S current, which was well fit using a m3h model, the persistent TTX-R current was not well fit by an m3h model and was better fit using an mh model. The persistent TTX-R current had a strong influence on resting potential, shifting it from -70 to -49.1 mV. Inclusion of an ultra-slow inactivation gate in the persistent current model reduced the potential shift only slightly, to -56.6 mV. The persistent TTX-R current also enhanced the response to depolarizing inputs that were subthreshold for spike electrogenesis. In addition, the presence of persistent TTX-R current predisposed the cell to anode break excitation. These results suggest that, while the persistent TTX-R current is not a major contributor to the rapid depolarizing phase of the action potential, it contributes to setting the electrogenic properties of small DRG neurons by modulating their resting potentials and response to subthreshold stimuli.

UR - http://www.scopus.com/inward/record.url?scp=0034843601&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034843601&partnerID=8YFLogxK

M3 - Article

C2 - 11535682

AN - SCOPUS:0034843601

VL - 86

SP - 1351

EP - 1364

JO - Journal of Neurophysiology

JF - Journal of Neurophysiology

SN - 0022-3077

IS - 3

ER -