Protein Kinase C Mediates Up-regulation of Tetrodotoxin-resistant, Persistent Na+ Current in Rat and Mouse Sensory Neurones

Overview

Journal J Physiol

Specialty Physiology

Date 2005 Jul 9

PMID 16002450

Citations 59

Authors

Mark D Baker

Affiliations

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Abstract

The tetrodotoxin-resistant (TTX-r) persistent Na(+) current, attributed to Na(V)1.9, was recorded in small (< 25 mum 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-gamma-S caused current up-regulation, an effect inhibited by the PKC pseudosubstrate inhibitor, PKC19-36. The current amplitude was also up-regulated by 25 microM 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 microM, 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.

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References

Khasar S, McCarter G, Levine J . Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors. J Neurophysiol. 1999; 81(3):1104-12. DOI: 10.1152/jn.1999.81.3.1104. View

Ueno S, Tsuda M, Iwanaga T, Inoue K . Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons. Br J Pharmacol. 1999; 126(2):429-36. PMC: 1565824. DOI: 10.1038/sj.bjp.0702319. View

Cesare P, Dekker L, Sardini A, Parker P, McNaughton P . Specific involvement of PKC-epsilon in sensitization of the neuronal response to painful heat. Neuron. 1999; 23(3):617-24. DOI: 10.1016/s0896-6273(00)80813-2. View

Akopian A, Souslova V, England S, Okuse K, Ogata N, Ure J . The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci. 1999; 2(6):541-8. DOI: 10.1038/9195. View

HODGKIN A, HUXLEY A . A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952; 117(4):500-44. PMC: 1392413. DOI: 10.1113/jphysiol.1952.sp004764. View

Priest B, Murphy B, Lindia J, Diaz C, Abbadie C, Ritter A . Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior. Proc Natl Acad Sci U S A. 2005; 102(26):9382-7. PMC: 1166597. DOI: 10.1073/pnas.0501549102. View

Black J, Waxman S . Molecular identities of two tetrodotoxin-resistant sodium channels in corneal axons. Exp Eye Res. 2002; 75(2):193-9. DOI: 10.1006/exer.2002.2014. View

Fang X, Djouhri L, Black J, Dib-Hajj S, Waxman S, Lawson S . The presence and role of the tetrodotoxin-resistant sodium channel Na(v)1.9 (NaN) in nociceptive primary afferent neurons. J Neurosci. 2002; 22(17):7425-33. PMC: 6757987. View

Carr R, Pianova S, Brock J . The effects of polarizing current on nerve terminal impulses recorded from polymodal and cold receptors in the guinea-pig cornea. J Gen Physiol. 2002; 120(3):395-405. PMC: 2229520. DOI: 10.1085/jgp.20028628. View

10.

Molliver D, Cook S, Carlsten J, Wright D, McCleskey E . ATP and UTP excite sensory neurons and induce CREB phosphorylation through the metabotropic receptor, P2Y2. Eur J Neurosci. 2002; 16(10):1850-60. DOI: 10.1046/j.1460-9568.2002.02253.x. View

11.

Rugiero F, Mistry M, Sage D, Black J, Waxman S, Crest M . Selective expression of a persistent tetrodotoxin-resistant Na+ current and NaV1.9 subunit in myenteric sensory neurons. J Neurosci. 2003; 23(7):2715-25. PMC: 6742082. View

12.

Baker M, Chandra S, Ding Y, Waxman S, Wood J . GTP-induced tetrodotoxin-resistant Na+ current regulates excitability in mouse and rat small diameter sensory neurones. J Physiol. 2003; 548(Pt 2):373-82. PMC: 2342858. DOI: 10.1113/jphysiol.2003.039131. View

13.

Carr R, Pianova S, Fernandez J, Fallon J, Belmonte C, Brock J . Effects of heating and cooling on nerve terminal impulses recorded from cold-sensitive receptors in the guinea-pig cornea. J Gen Physiol. 2003; 121(5):427-39. PMC: 2217380. DOI: 10.1085/jgp.200308814. View

14.

Kiernan M, Baker M, Bostock H . Characteristics of late Na(+) current in adult rat small sensory neurons. Neuroscience. 2003; 119(3):653-60. DOI: 10.1016/s0306-4522(03)00194-5. View

15.

Moriyama T, Iida T, Kobayashi K, Higashi T, Fukuoka T, Tsumura H . Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity. J Neurosci. 2003; 23(14):6058-62. PMC: 6740351. View

16.

Huang H, Wu X, Nicol G, Meller S, Vasko M . ATP augments peptide release from rat sensory neurons in culture through activation of P2Y receptors. J Pharmacol Exp Ther. 2003; 306(3):1137-44. DOI: 10.1124/jpet.103.052951. View

17.

Bostock H, Campero M, Serra J, Ochoa J . Velocity recovery cycles of C fibres innervating human skin. J Physiol. 2003; 553(Pt 2):649-63. PMC: 2343583. DOI: 10.1113/jphysiol.2003.046342. View

18.

Stucky C, Medler K, Molliver D . The P2Y agonist UTP activates cutaneous afferent fibers. Pain. 2004; 109(1-2):36-44. DOI: 10.1016/j.pain.2004.01.007. View

19.

Rush A, Waxman S . PGE2 increases the tetrodotoxin-resistant Nav1.9 sodium current in mouse DRG neurons via G-proteins. Brain Res. 2004; 1023(2):264-71. DOI: 10.1016/j.brainres.2004.07.042. View

20.

Bostock H, Baker M, Reid G . Changes in excitability of human motor axons underlying post-ischaemic fasciculations: evidence for two stable states. J Physiol. 1991; 441:537-57. PMC: 1180213. DOI: 10.1113/jphysiol.1991.sp018766. View