Sodium channel beta2 subunits regulate tetrodotoxin-sensitive sodium channels in small dorsal root ganglion neurons and modulate the response to pain

Details

Serval ID
serval:BIB_8862AEAD8799
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sodium channel beta2 subunits regulate tetrodotoxin-sensitive sodium channels in small dorsal root ganglion neurons and modulate the response to pain
Journal
Journal of Neuroscience
Author(s)
Lopez-Santiago  L. F., Pertin  M., Morisod  X., Chen  C., Hong  S., Wiley  J., Decosterd  I., Isom  L. L.
ISSN
1529-2401 (Electronic)
Publication state
Published
Issued date
07/2006
Volume
26
Number
30
Pages
7984-94
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S. --- Old month value: Jul 26
Abstract
Voltage-gated sodium channel (Na(v)1) beta2 subunits modulate channel gating, assembly, and cell-surface expression in CNS neurons in vitro and in vivo. beta2 expression increases in sensory neurons after nerve injury, and development of mechanical allodynia in the spared nerve injury model is attenuated in beta2-null mice. Thus, we hypothesized that beta2 modulates electrical excitability in dorsal root ganglion (DRG) neurons in vivo. We compared sodium currents (I(Na)) in small DRG neurons from beta2+/+ and beta2-/- mice to determine the effects of beta2 on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na(v)1 in vivo. Small-fast DRG neurons acutely isolated from beta2-/- mice showed significant decreases in TTX-S I(Na) compared with beta2+/+ neurons. This decrease included a 51% reduction in maximal sodium conductance with no detectable changes in the voltage dependence of activation or inactivation. TTX-S, but not TTX-R, I(Na) activation and inactivation kinetics in these cells were slower in beta2(-/-) mice compared with controls. The selective regulation of TTX-S I(Na) was supported by reductions in transcript and protein levels of TTX-S Na(v)1s, particularly Na(v)1.7. Low-threshold mechanical sensitivity was preserved in beta2-/- mice, but they were more sensitive to noxious thermal stimuli than wild type whereas their response during the late phase of the formalin test was attenuated. Our results suggest that beta2 modulates TTX-S Na(v)1 mRNA and protein expression resulting in increased TTX-S I(Na) and increases the rates of TTX-S Na(v)1 activation and inactivation in small-fast DRG neurons in vivo. TTX-R I(Na) were not significantly modulated by beta2.
Keywords
Adaptation, Physiological/drug effects/physiology Animals Cells, Cultured Dose-Response Relationship, Drug Ganglia, Spinal/drug effects/*physiology Ion Channel Gating/drug effects/*physiology Mice Mice, Inbred C57BL Mice, Knockout Nerve Tissue Proteins/*metabolism Neurons/drug effects/*physiology Pain Threshold/drug effects/*physiology Sodium Channels/*metabolism Tetrodotoxin/*administration & dosage
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 10:45
Last modification date
20/08/2019 14:47
Usage data