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PGE2 increases the tetrodotoxin-resistant Nav1.9 sodium current in mouse DRG neurons via G-proteins.
- Source :
-
Brain research [Brain Res] 2004 Oct 15; Vol. 1023 (2), pp. 264-71. - Publication Year :
- 2004
-
Abstract
- Inflammation caused by tissue damage results in pain, reflecting an increase in excitability of the primary afferent neurons innervating the area. There is some evidence to suggest that altered function of voltage-gated sodium channels is responsible for the hyperexcitability produced by inflammatory agents, possibly acting through G-proteins, but the role of different channel subtypes has not been fully explored. The tetrodotoxin-resistant (TTX-R) sodium channel Na(v)1.9 is expressed selectively in C- and A-fibre nociceptive-type units and is upregulated by G-protein activation. In this study, we examined the effects of the inflammatory agent prostaglandin-E(2) (PGE(2)) on Na(v)1.9 current in both Na(v)1.8-null and wild-type (WT) mice and explored the role of specific G-proteins in modulation. PGE(2) caused a twofold increase in Na(v)1.9 current (p<0.05) in both systems. Steady-state activation was shifted in a hyperpolarizing direction by 6-8 mV and availability of channels by 12 mV. No differences in the activation and inactivation kinetics could be detected. The increase in current was blocked by pertussis toxin (PTX) but not cholera toxin (CTX), showing involvement of G(i/o) but not G(s) subunits. Our data indicate that Na(v)1.9 current can be increased during inflammation via a G-protein dependent mechanism and suggest that this could contribute to the regulation of electrogenesis in dorsal root ganglia (DRG) neurons.
- Subjects :
- Animals
Cells, Cultured
Cholera Toxin pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Electric Conductivity
Membrane Potentials drug effects
Mice
NAV1.9 Voltage-Gated Sodium Channel
Neurons physiology
Neuropeptides drug effects
Patch-Clamp Techniques methods
Pertussis Toxin pharmacology
Serotonin pharmacology
Sodium Channels drug effects
Dinoprostone pharmacology
GTP-Binding Proteins physiology
Ganglia, Spinal cytology
Neurons drug effects
Neuropeptides physiology
Sodium Channels physiology
Tetrodotoxin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-8993
- Volume :
- 1023
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 15374752
- Full Text :
- https://doi.org/10.1016/j.brainres.2004.07.042