title: Regulation of the spontaneous augmentation of Na(V)1.9 in mouse dorsal root ganglion neurons: effect of PKA and PKC pathways.
abstract: Sensory neurons in the dorsal root ganglion express two kinds of tetrodotoxin resistant (TTX-R) isoforms of voltage-gated sodium channels, Na(V)1.8 and Na(V)1.9. These isoforms play key roles in the pathophysiology of chronic pain. Of special interest is Na(V)1.9: our previous studies revealed a unique property of the Na(V)1.9 current, i.e., the Na(V)1.9 current shows a gradual and notable up-regulation of the peak amplitude during recording ("spontaneous augmentation of Na(V)1.9"). However, the mechanism underlying the spontaneous augmentation of Na(V)1.9 is still unclear. In this study, we examined the effects of protein kinases A and C (PKA and PKC), on the spontaneous augmentation of Na(V)1.9. The spontaneous augmentation of the Na(V)1.9 current was significantly suppressed by activation of PKA, whereas activation of PKA did not affect the voltage dependence of inactivation for the Na(V)1.9 current. On the contrary, the finding that activation of PKC can affect the voltage dependence of inactivation for Na(V)1.9 in the perforated patch recordings, where the augmentation does not occur, suggests that the effects of PMA are independent of the augmentation process. These results indicate that the spontaneous augmentation of Na(V)1.9 was regulated directly by PKA, and indirectly by PKC.
authors.affiliation: Technical Center, Hiroshima University, Hiroshima 734-8551, Japan. kakimura@hiroshima-u.ac.jp
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kakimura
authors.forename: Taixing
authors.initials: T
authors.lastname: Zheng
authors.forename: Noriko
authors.initials: N
authors.lastname: Uryu
authors.forename: Nobukuni
authors.initials: N
authors.lastname: Ogata
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000378:metabolism*; D051379:Mice; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
chemical_list: D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D015222:Sodium Channels; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C
references.citation: Pflugers Arch. 2006 Oct;453(1):83-96
references.pmid: 16838161
references.citation: J Gen Physiol. 1996 Nov;108(5):375-9
references.pmid: 8923263
references.citation: Genomics. 1999 Aug 1;59(3):309-18
references.pmid: 10444332
references.citation: Expert Rev Neurother. 2007 Nov;7(11):1597-612
references.pmid: 17997706
references.citation: Mol Cell Neurosci. 2002 Sep;21(1):63-80
references.pmid: 12359152
references.citation: J Physiol. 1999 Jul 15;518 ( Pt 2):371-84
references.pmid: 10381586
references.citation: Pflugers Arch. 2004 Oct;449(1):76-87
references.pmid: 15290301
references.citation: Neuroscience. 2001;104(3):875-90
references.pmid: 11440817
references.citation: J Neurosci. 2001 Sep 1;21(17):6933-9
references.pmid: 11517280
references.citation: J Physiol. 2003 Apr 15;548(Pt 2):373-82
references.pmid: 12651922
references.citation: Trends Pharmacol Sci. 2005 Oct;26(10):496-502
references.pmid: 16125256
references.citation: J Neurosci. 1994 Jul;14(7):4226-36
references.pmid: 8027774
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9382-7
references.pmid: 15964986
references.citation: Neuron. 1999 Sep;24(1):253-60
references.pmid: 10677042
references.citation: Neurosci Lett. 2004 Jan 23;355(1-2):45-8
references.pmid: 14729231
references.citation: Nat Neurosci. 1999 Jun;2(6):541-8
references.pmid: 10448219
references.citation: J Neurosci. 2003 Apr 1;23(7):2715-25
references.pmid: 12684457
references.citation: Neuroscience. 1999;88(4):1267-74
references.pmid: 10336135
references.citation: J Neurosci. 2000 Jun 15;20(12):4680-5
references.pmid: 10844037
references.citation: Pain. 2008 Mar;135(1-2):31-6
references.pmid: 17544210
references.citation: J Physiol. 1993 Apr;463:39-56
references.pmid: 8246189
references.citation: Science. 1991 Oct 4;254(5028):115-8
references.pmid: 1656525
references.citation: J Neurophysiol. 2001 Sep;86(3):1351-64
references.pmid: 11535682
references.citation: J Biol Chem. 1993 Dec 25;268(36):27355-62
references.pmid: 8262976
references.citation: J Gen Physiol. 1988 Aug;92(2):145-59
references.pmid: 2459299
references.citation: J Pharmacol Sci. 2007 Jan;103(1):93-102
references.pmid: 17220592
references.citation: J Physiol. 2005 Sep 15;567(Pt 3):851-67
references.pmid: 16002450
references.citation: J Neurosci. 1999 Dec 15;19(24):RC43
references.pmid: 10594087
references.citation: J Neurophysiol. 2004 Apr;91(4):1556-69
references.pmid: 14657190
references.citation: Pflugers Arch. 1981 Aug;391(2):85-100
references.pmid: 6270629
references.citation: Neuron. 1992 Jun;8(6):1151-9
references.pmid: 1319185
references.citation: Mol Cell Neurosci. 2004 May;26(1):123-34
references.pmid: 15121184
references.citation: J Physiol. 1993 Jul;466:9-37
references.pmid: 8410717
references.citation: Circ Res. 2002 Mar 8;90(4):E49-57
references.pmid: 11884381
references.citation: Am J Physiol Cell Physiol. 2000 Apr;278(4):C638-45
references.pmid: 10751312
references.citation: Science. 1991 Nov 8;254(5033):866-8
references.pmid: 1658937
references.citation: J Neurophysiol. 2001 Aug;86(2):629-40
references.pmid: 11495938
references.citation: Br J Pharmacol. 1999 Jun;127(3):671-8
references.pmid: 10401557
references.citation: Eur J Pharmacol. 2004 Oct 6;501(1-3):87-94
references.pmid: 15464066