title: Sustained increase in the excitability of myelinated peripheral axons to depolarizing current is mediated by Nav1.6.
abstract: Changes in the excitability of peripheral myelinated axons in response to long-lasting subthreshold depolarizing or hyperpolarizing currents (threshold electrotonus) are used as a complementary electrophysiological parameter in the study of peripheral nerve diseases in people. However, the contribution made by various axonal ion channels to specific components of threshold electrotonus remains incompletely understood. In this study, we have recorded threshold electrotonus responses from isolated nerve segments of sural nerve from control and Scn8amed mice, which lack functional Nav1.6 voltage-gated sodium channel. In med mice, the increase in axonal excitability produced by application of subthreshold depolarizing currents for 100-200ms was not sustained. In contrast, there was no difference in threshold electrotonus responses to subthreshold hyperpolarizing current application between Scn8amed and control mice. These data reveal the specific functional role of an identified subtype of voltage-gated sodium channel (Nav1.6) in mediating the depolarizing threshold electrotonus response of peripheral myelinated nerve fibers.
authors.affiliation: Institute of Physiology, University of Munich, Pettenkoferstr. 12, D-80336 Munich, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Sittl
authors.forename: Richard W
authors.initials: RW
authors.lastname: Carr
authors.forename: Peter
authors.initials: P
authors.lastname: Grafe
mesh_terms: D000200:Action Potentials / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000502:physiology*; D015640:Ion Channel Gating / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009431:Neural Conduction / Q000235:genetics*; D009924:Organ Culture Techniques; D010525:Peripheral Nerves / Q000502:physiology*; D015222:Sodium Channels / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D015222:Sodium Channels