title: Gating and modulation of presumptive NaV1.9 channels in enteric and spinal sensory neurons.
abstract: The NaV1.9 subunit is expressed in nociceptive dorsal root ganglion (DRG) neurons and sensory myenteric neurons in which it generates 'persistent' tetrodotoxin-resistant (TTX-R) Na+ currents of yet unknown physiological functions. Here, we have analyzed these currents in details by combining single-channel and whole-cell recordings from cultured rat DRG and myenteric neurons. Comparison of single-channel with whole-cell data indicates that recording using internal CsCl best reflects the basic electrical features of NaV1.9 currents. Inclusion of fluoride in the pipette solution caused a negative shift in the activation and inactivation gates of NaV1.9 but not NaV1.8. Fluoride acts by promoting entry of NaV1.9 channels into a preopen closed state, which causes a strong bias towards opening and enhances the ability of sensory neurons to sustain spiking. Thus, the modulation of the resting-closed states of NaV1.9 channels strongly influences nociceptor excitability and may provide a mechanism by which inflammatory mediators alter pain threshold.
authors.affiliation: Intégration des Informations Sensorielles, CNRS, UMR 6150, Faculté de Médecine, IFR Jean Roche, 13916 Marseille 20, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coste
authors.forename: Nancy
authors.initials: N
authors.lastname: Osorio
authors.forename: Françoise
authors.initials: F
authors.lastname: Padilla
authors.forename: Marcel
authors.initials: M
authors.lastname: Crest
authors.forename: Patrick
authors.initials: P
authors.lastname: Delmas
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D005725:Ganglia, Autonomic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002712:Chlorides; D018836:Inflammation Mediators; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C113705:Scn11a protein, rat; D015222:Sodium Channels; D002586:Cesium; C028019:cesium chloride; D005459:Fluorides