Differential contribution of sodium channel subtypes to action potential generation in unmyelinated human C-type nerve fibers.
BACKGROUND
Multiple voltage-dependent sodium channels (Na(v)) contribute to action potentials and excitability of primary nociceptive neurons. The aim of the current study was to characterize subtypes of Na(v) that contribute to action potential generation in peripheral unmyelinated human C-type nerve fibers.


METHODS
Registration of C-fiber compound action potentials and determination of membrane threshold was performed by a computerized threshold tracking program. Nerve fibers were stimulated with a 1-ms current pulse either alone or after a small ramp current lasting 300 ms.


RESULTS
Compound C-fiber action potentials elicited by supramaximal 1-ms current pulses were rather resistant to application of tetrodotoxin (30-90 nM). However, the same concentrations of tetrodotoxin strongly reduced the peak height and elevated membrane threshold of action potentials evoked at the end of a 300-ms current ramp. A similar effect was observed during application of lidocaine and mexiletine (50 microM each).


CONCLUSIONS
These data indicate that more than one type of Na(v) contributes to the generation of action potentials in unmyelinated human C-type nerve fibers. The peak height of an action potential produced by a short electrical impulse is dependent on the activation of tetrodotoxin-resistant ion channels. In contrast, membrane threshold and action potential peak height at the end of a slow membrane depolarization are regulated by a subtype of Na(v) with high sensitivity to low concentrations of tetrodotoxin, lidocaine, and mexiletine. The electrophysiologic and pharmacologic characteristics may indicate the functional activity of the Na(v) 1.7 subtype of voltage-dependent sodium channels.
Lang
Philip M
PM
Department of Anesthesiology, University of Munich, Munich, Germany. Philip.Lang@med.uni-muenchen.de
Hilmer
Verena B
VB
Grafe
Peter
P
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004594:Electrophysiology / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008801:Mexiletine / Q000008:administration & dosage / Q000494:pharmacology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology*; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000008:administration & dosage / Q000494:pharmacology
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D008801:Mexiletine; D013779:Tetrodotoxin; D008012:Lidocaine