Sodium currents of large (Aβ-type) adult cutaneous afferent dorsal root ganglion neurons display rapid recovery from inactivation before and after axotomy

B. Everill, Theodore Cummins, S. G. Waxman, J. D. Kocsis

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Voltage-dependent Na-currents were studied, using whole cell voltage clamp, in acutely dissociated, large (mostly Aβ-fiber type) cutaneous afferent dorsal root ganglia neurons (L4 and L5) from the adult rat. Cells were dissociated 14-17 days after axotomy. Control and axotomized neurons were identified via the retrograde marker hydroxy-stilbamide (fluorogold) which was injected into the lateral and plantar region of the skin of the foot and were studied using whole cell patch clamp techniques within 12-20 h of dissociation and plating. Cells were dissociated 14-17 days after injury. Both control and axotomized neurons displayed complex Na-currents composed of components with distinct kinetic and pharmacological properties. The large (48-50 μm diameter) control cutaneous afferent neurons, many of which likely give rise to myelinated Aβ-fibers, exhibited Na-currents with both slow and fast inactivating kinetics. The fast inactivating current in large cutaneous afferent dorsal root ganglion neurons was tetrodotoxin-sensitive and recovered from inactivation ∼four-fold faster at -60 mV (P <0.001) and ∼six-fold faster at -70 mV (P <0.001) than the tetrodotoxin-sensitive current in small (<30 μm diameter) neurons. Further, while the tetrodotoxin-sensitive currents in smaller dorsal root ganglion neurons (mainly C-fiber type) reprime approximately four-fold faster following peripheral axotomy, repriming of the fast inactivating current in larger cutaneous afferent neurons was not significantly altered following axotomy. However, while 77% of control large neurons were observed to express the slower inactivating, tetrodotoxin-resistant current, only 45% of these large neurons did after axotomy. These results indicate that large adult cutaneous afferent dorsal root ganglion neurons (Aβ-type) express tetrodotoxin-sensitive Na-currents, which have much faster repriming than Na-currents in small (C-type) neurons, both before, and after axotomy. Like small neurons, the majority of large neurons downregulate the tetrodotoxin-resistant current following sciatic nerve section.

Original languageEnglish (US)
Pages (from-to)161-169
Number of pages9
JournalNeuroscience
Volume106
Issue number1
DOIs
StatePublished - Sep 3 2001
Externally publishedYes

Fingerprint

Axotomy
Spinal Ganglia
Sodium
Neurons
Skin
Tetrodotoxin
Myelinated Nerve Fibers
Afferent Neurons
Unmyelinated Nerve Fibers
Patch-Clamp Techniques
Sciatic Nerve
Foot
Down-Regulation

Keywords

  • Axotomy
  • Cutaneous afferents
  • Fast repriming current
  • Nerve crush
  • Sodium channels
  • Tail currents

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sodium currents of large (Aβ-type) adult cutaneous afferent dorsal root ganglion neurons display rapid recovery from inactivation before and after axotomy. / Everill, B.; Cummins, Theodore; Waxman, S. G.; Kocsis, J. D.

In: Neuroscience, Vol. 106, No. 1, 03.09.2001, p. 161-169.

Research output: Contribution to journalArticle

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abstract = "Voltage-dependent Na-currents were studied, using whole cell voltage clamp, in acutely dissociated, large (mostly Aβ-fiber type) cutaneous afferent dorsal root ganglia neurons (L4 and L5) from the adult rat. Cells were dissociated 14-17 days after axotomy. Control and axotomized neurons were identified via the retrograde marker hydroxy-stilbamide (fluorogold) which was injected into the lateral and plantar region of the skin of the foot and were studied using whole cell patch clamp techniques within 12-20 h of dissociation and plating. Cells were dissociated 14-17 days after injury. Both control and axotomized neurons displayed complex Na-currents composed of components with distinct kinetic and pharmacological properties. The large (48-50 μm diameter) control cutaneous afferent neurons, many of which likely give rise to myelinated Aβ-fibers, exhibited Na-currents with both slow and fast inactivating kinetics. The fast inactivating current in large cutaneous afferent dorsal root ganglion neurons was tetrodotoxin-sensitive and recovered from inactivation ∼four-fold faster at -60 mV (P <0.001) and ∼six-fold faster at -70 mV (P <0.001) than the tetrodotoxin-sensitive current in small (<30 μm diameter) neurons. Further, while the tetrodotoxin-sensitive currents in smaller dorsal root ganglion neurons (mainly C-fiber type) reprime approximately four-fold faster following peripheral axotomy, repriming of the fast inactivating current in larger cutaneous afferent neurons was not significantly altered following axotomy. However, while 77{\%} of control large neurons were observed to express the slower inactivating, tetrodotoxin-resistant current, only 45{\%} of these large neurons did after axotomy. These results indicate that large adult cutaneous afferent dorsal root ganglion neurons (Aβ-type) express tetrodotoxin-sensitive Na-currents, which have much faster repriming than Na-currents in small (C-type) neurons, both before, and after axotomy. Like small neurons, the majority of large neurons downregulate the tetrodotoxin-resistant current following sciatic nerve section.",
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AB - Voltage-dependent Na-currents were studied, using whole cell voltage clamp, in acutely dissociated, large (mostly Aβ-fiber type) cutaneous afferent dorsal root ganglia neurons (L4 and L5) from the adult rat. Cells were dissociated 14-17 days after axotomy. Control and axotomized neurons were identified via the retrograde marker hydroxy-stilbamide (fluorogold) which was injected into the lateral and plantar region of the skin of the foot and were studied using whole cell patch clamp techniques within 12-20 h of dissociation and plating. Cells were dissociated 14-17 days after injury. Both control and axotomized neurons displayed complex Na-currents composed of components with distinct kinetic and pharmacological properties. The large (48-50 μm diameter) control cutaneous afferent neurons, many of which likely give rise to myelinated Aβ-fibers, exhibited Na-currents with both slow and fast inactivating kinetics. The fast inactivating current in large cutaneous afferent dorsal root ganglion neurons was tetrodotoxin-sensitive and recovered from inactivation ∼four-fold faster at -60 mV (P <0.001) and ∼six-fold faster at -70 mV (P <0.001) than the tetrodotoxin-sensitive current in small (<30 μm diameter) neurons. Further, while the tetrodotoxin-sensitive currents in smaller dorsal root ganglion neurons (mainly C-fiber type) reprime approximately four-fold faster following peripheral axotomy, repriming of the fast inactivating current in larger cutaneous afferent neurons was not significantly altered following axotomy. However, while 77% of control large neurons were observed to express the slower inactivating, tetrodotoxin-resistant current, only 45% of these large neurons did after axotomy. These results indicate that large adult cutaneous afferent dorsal root ganglion neurons (Aβ-type) express tetrodotoxin-sensitive Na-currents, which have much faster repriming than Na-currents in small (C-type) neurons, both before, and after axotomy. Like small neurons, the majority of large neurons downregulate the tetrodotoxin-resistant current following sciatic nerve section.

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