GTP gamma S increases Nav1.8 current in small-diameter dorsal root ganglia neurons - PubMed (original) (raw)

GTP gamma S increases Nav1.8 current in small-diameter dorsal root ganglia neurons

Carl Y Saab et al. Exp Brain Res. 2003 Oct.

Abstract

Tetrodotoxin-resistant (TTX-R) sodium current in small-size dorsal root ganglia (DRG) neurons is upregulated by prostaglandin E(2) and serotonin through a protein kinase A (PKA)/protein kinase (PKC) pathway, suggesting G protein modulation of one or more TTX-R channels in these neurons. Recently, GTP(gammaS), a hydrolysis-resistant analogue of GTP, was shown to increase the persistent current produced by the TTX-R Na(v)1.9. In this study, we investigated the modulation of another TTX-R channel, Na(v)1.8, by GTP(gammaS) in small-diameter DRG neurons from rats using whole-cell voltage clamp recordings. Because it has been suggested that fluoride, often used in intracellular recording solutions, may bind to trace amounts of aluminum and activate G proteins, we recorded Na(v)1.8 currents with and without intracellular fluoride, and with the addition of deferoxamine, an aluminum chelator, to prevent fluoride-aluminum binding. Our results show that GTP(gammaS) (100 micro M) caused a significant increase in Na(v)1.8 current (67%) with a chloride-based intracellular solution. Although the inclusion of fluoride instead of chloride in the pipette solution increased the Na(v)1.8 current by 177%, GTP(gammaS) further increased Na(v)1.8 current by 67% under these conditions. While the effect of GTP(gammaS) was prevented by pretreatment with H7 (100 micro M), a non-selective PKA/PKC inhibitor, the fluoride-induced increase in Na(v)1.8 current was not sensitive to H7 (100 micro M), or to inclusion of deferoxamine (1 mM) in the intracellular solution. We conclude that G protein activation by GTP(gammaS) increases Na(v)1.8 current through a PKA/PKC mechanism and that addition of fluoride to the pipette solution further enhances the current, but is not a confounding variable in the study of Na(v)1.8 channel modulation by G proteins independent of a PKA/PKC pathway or binding to aluminum.

PubMed Disclaimer

Similar articles

• Multiple types of Na(+) currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia.
  Matsutomi T, Nakamoto C, Zheng T, Kakimura J, Ogata N. Matsutomi T, et al. Pflugers Arch. 2006 Oct;453(1):83-96. doi: 10.1007/s00424-006-0104-3. Epub 2006 Jul 13. Pflugers Arch. 2006. PMID: 16838161
• Protein kinase C mediates up-regulation of tetrodotoxin-resistant, persistent Na+ current in rat and mouse sensory neurones.
  Baker MD. Baker MD. J Physiol. 2005 Sep 15;567(Pt 3):851-67. doi: 10.1113/jphysiol.2005.089771. Epub 2005 Jul 7. J Physiol. 2005. PMID: 16002450 Free PMC article.
• The chemokine CCL2 increases Nav1.8 sodium channel activity in primary sensory neurons through a Gβγ-dependent mechanism.
  Belkouch M, Dansereau MA, Réaux-Le Goazigo A, Van Steenwinckel J, Beaudet N, Chraibi A, Melik-Parsadaniantz S, Sarret P. Belkouch M, et al. J Neurosci. 2011 Dec 14;31(50):18381-90. doi: 10.1523/JNEUROSCI.3386-11.2011. J Neurosci. 2011. PMID: 22171040 Free PMC article.
• Dexmedetomidine inhibits Tetrodotoxin-resistant Nav1.8 sodium channel activity through Gi/o-dependent pathway in rat dorsal root ganglion neurons.
  Gu XY, Liu BL, Zang KK, Yang L, Xu H, Pan HL, Zhao ZQ, Zhang YQ. Gu XY, et al. Mol Brain. 2015 Mar 3;8:15. doi: 10.1186/s13041-015-0105-2. Mol Brain. 2015. PMID: 25761941 Free PMC article.
• Modulation of sodium channels in primary afferent neurons.
  Bevan S, Storey N. Bevan S, et al. Novartis Found Symp. 2002;241:144-53; discussion 153-8, 226-32. Novartis Found Symp. 2002. PMID: 11771643 Review.

Cited by

• PKCε phosphorylation of the sodium channel NaV1.8 increases channel function and produces mechanical hyperalgesia in mice.
  Wu DF, Chandra D, McMahon T, Wang D, Dadgar J, Kharazia VN, Liang YJ, Waxman SG, Dib-Hajj SD, Messing RO. Wu DF, et al. J Clin Invest. 2012 Apr;122(4):1306-15. doi: 10.1172/JCI61934. Epub 2012 Mar 19. J Clin Invest. 2012. PMID: 22426212 Free PMC article.
• Multiple types of Na(+) currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia.
  Matsutomi T, Nakamoto C, Zheng T, Kakimura J, Ogata N. Matsutomi T, et al. Pflugers Arch. 2006 Oct;453(1):83-96. doi: 10.1007/s00424-006-0104-3. Epub 2006 Jul 13. Pflugers Arch. 2006. PMID: 16838161
• Voltage-clamp and current-clamp recordings from mammalian DRG neurons.
  Cummins TR, Rush AM, Estacion M, Dib-Hajj SD, Waxman SG. Cummins TR, et al. Nat Protoc. 2009;4(8):1103-12. doi: 10.1038/nprot.2009.91. Epub 2009 Jul 9. Nat Protoc. 2009. PMID: 19617882
• The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity.
  Amaya F, Wang H, Costigan M, Allchorne AJ, Hatcher JP, Egerton J, Stean T, Morisset V, Grose D, Gunthorpe MJ, Chessell IP, Tate S, Green PJ, Woolf CJ. Amaya F, et al. J Neurosci. 2006 Dec 13;26(50):12852-60. doi: 10.1523/JNEUROSCI.4015-06.2006. J Neurosci. 2006. PMID: 17167076 Free PMC article.
• Activated polymorphonuclear cells promote injury and excitability of dorsal root ganglia neurons.
  Shaw SK, Owolabi SA, Bagley J, Morin N, Cheng E, LeBlanc BW, Kim M, Harty P, Waxman SG, Saab CY. Shaw SK, et al. Exp Neurol. 2008 Apr;210(2):286-94. doi: 10.1016/j.expneurol.2007.11.024. Epub 2007 Dec 4. Exp Neurol. 2008. PMID: 18201702 Free PMC article.

References

1. 1. J Physiol. 1996 Sep 1;495 ( Pt 2):429-40 - PubMed
2. 1. Eur J Neurosci. 2001 Feb;13(3):545-52 - PubMed
3. 1. Prog Brain Res. 1993;99:309-24 - PubMed
4. 1. Neuroscience. 1996 Oct;74(4):1175-85 - PubMed
5. 1. J Neurophysiol. 2000 Mar;83(3):1273-82 - PubMed

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.
  • Springer

• Molecular Biology Databases

  • Guide to Pharmacology