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Protein kinase C mediates up-regulation of tetrodotoxin-resistant, persistent Na+ current in rat and mouse sensory neurones.

Authors :
Baker, Mark D.
Source :
Journal of Physiology. Sep2005, Vol. 567 Issue 3, p851-867. 17p. 9 Diagrams, 1 Chart.
Publication Year :
2005

Abstract

The tetrodotoxin-resistant (TTX-r) persistent Na+ current, attributed to NaV1.9, was recorded in small (< 25 μm apparent diameter) dorsal root ganglion (DRG) neurones cultured from P21 rats and from adult wild-type and NaV1.8 null mice. In conventional whole-cell recordings intracellular GTP-γ-S caused current up-regulation, an effect inhibited by the PKC pseudosubstrate inhibitor, PKC19–36. The current amplitude was also up-regulated by 25 μ m intracellular 1-oleoyl-2-acetyl-sn-glycerol (OAG) consistent with PKC involvement. In perforated-patch recordings, phorbol 12-myristate 13-acetate (PMA) up-regulated the current, whereas membrane-permeant activators of protein kinase A (PKA) were without effect. PGE2 did not acutely up-regulate the current. Conversely, both PGE2 and PKA activation up-regulated the major TTX-r Na+ current, NaV1.8. Extracellular ATP up-regulated the persistent current with an average apparent Kd near 13 μ m, possibly consistent with P2Y receptor activation. Numerical simulation of the up-regulation qualitatively reproduced changes in sensory neurone firing properties. The activation of PKC appears to be a necessary step in the GTP-dependent up-regulation of persistent Na+ current. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00223751
Volume :
567
Issue :
3
Database :
Academic Search Index
Journal :
Journal of Physiology
Publication Type :
Academic Journal
Accession number :
18188347
Full Text :
https://doi.org/10.1113/jphysiol.2005.089771