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Protein kinase C mediates up‐regulation of tetrodotoxin‐resistant, persistent Na + current in rat and mouse sensory neurones
Author(s) -
Baker Mark D.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.089771
Subject(s) - protein kinase c , tetrodotoxin , dorsal root ganglion , gtp' , intracellular , extracellular , biophysics , chemistry , protein kinase a , medicine , endocrinology , patch clamp , sensory neuron , microbiology and biotechnology , receptor , biology , kinase , biochemistry , neuroscience , sensory system , enzyme
The tetrodotoxin‐resistant (TTX‐r) persistent Na + current, attributed to Na V 1.9, was recorded in small (< 25 μm apparent diameter) dorsal root ganglion (DRG) neurones cultured from P21 rats and from adult wild‐type and Na V 1.8 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. PGE 2 did not acutely up‐regulate the current. Conversely, both PGE 2 and PKA activation up‐regulated the major TTX‐r Na + current, Na V 1.8. Extracellular ATP up‐regulated the persistent current with an average apparent K d 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.