Gating and modulation of presumptive NaV1.9 channels in enteric and spinal sensory neurons.
Mol Cell Neurosci
; 26(1): 123-34, 2004 May.
Article
in En
| MEDLINE
| ID: mdl-15121184
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neuropeptides
/
Sodium Channels
/
Ion Channel Gating
/
Ganglia, Autonomic
/
Ganglia, Spinal
/
Myenteric Plexus
/
Neurons, Afferent
Limits:
Animals
Language:
En
Journal:
Mol Cell Neurosci
Journal subject:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Year:
2004
Document type:
Article
Affiliation country: