Selective Expression of a Persistent Tetrodotoxin-Resistant Na+Current and NaV1.9 Subunit in Myenteric Sensory Neurons
| Autor: | Maurice Gola, Joel A. Black, Marcel Crest, Dominique Sage, Patrick Delmas, Stephen G. Waxman, Nadine Clerc, M. Mistry, Francois Rugiero |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Patch-Clamp Techniques
Transcription Genetic Protein subunit Guinea Pigs Molecular Sequence Data Action Potentials Myenteric Plexus Sensory system Tetrodotoxin Sodium Channels Nav1.9 Guinea pig Dorsal root ganglion medicine Animals Amino Acid Sequence Neurons Afferent RNA Messenger ARTICLE NAV1.9 Voltage-Gated Sodium Channel Cells Cultured Reverse Transcriptase Polymerase Chain Reaction Chemistry musculoskeletal neural and ocular physiology General Neuroscience Neuropeptides Electric Conductivity Depolarization Immunohistochemistry Rats Kinetics Protein Subunits medicine.anatomical_structure nervous system Biophysics Enteric nervous system Sequence Alignment Neuroscience Intracellular Cadmium |
| Zdroj: | The Journal of Neuroscience. 23:2715-2725 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Voltage-gated Na+currents play critical roles in shaping electrogenesis in neurons. Here, we have identified a TTX-resistant Na+current (TTX-RINa) in duodenum myenteric neurons of guinea pig and rat and have sought evidence regarding the molecular identity of the channel producing this current from the expression of Na+channel α subunits and the biophysical and pharmacological properties of TTX-RINa. Whole-cell patch-clamp recording fromin situneurons revealed the presence of a voltage-gated Na+current that was highly resistant to TTX (IC50, ∼200 μm) and selectively distributed in myenteric sensory neurons but not in interneurons and motor neurons. TTX-RINaactivated slowly in response to depolarization and exhibited a threshold for activation at –50 mV. V1/2values of activation and steady-state inactivation were –32 and –31 mV in the absence of fluoride, respectively, which, as predicted from the window current, generated persistent currents. TTX-RINaalso had prominent ultraslow inactivation, which turns off 50% of the conductance at rest (–60 mV). Substituting CsF for CsCl in the intracellular solution shifted the voltage-dependent parameters of TTX-RINaleftward by ∼20 mV. Under these conditions, TTX-RINahad voltage-dependent properties similar to those reported previously for NaN/NaV1.9 in dorsal root ganglion neurons. Consistent with this, reverse transcription-PCR, single-cell profiling, and immunostaining experiments indicated that NaV1.9 transcripts and subunits, but not NaV1.8, were expressed in the enteric nervous system and restricted to myenteric sensory neurons. TTX-RINamay play an important role in regulating subthreshold electrogenesis and boosting synaptic stimuli, thereby conferring distinct integrative properties to myenteric sensory neurons. |
| Databáze: | OpenAIRE |
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