| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Medicine, Laval University, Sainte-Foy, PQ, Canada
2 Molecular and Cellular Cardiology, Suny Downstate Medical Center, New York, NY, USA
* To whom correspondence should be addressed. E-mail: mohamed.chahine{at}phc.ulaval.ca.
Voltage-gated Na+ channels (VGSC) are transmembrane proteins that are essential for the initiation and propagation of action potentials in neuronal excitability. Because neurons express a mixture of Na+ channel isoforms and PKC isozymes, the nature of which channel is being regulated by which PKC isozyme is not known. We showed that DRG VGSC Nav1.7 (TTX-sensitive) and Nav1.8 (TTX-resistant), expressed in Xenopus oocytes were differentially regulated by PKA and PKC isozymes using the two-electrode voltage clamp method. PKA activation resulted in a dose-dependent potentiation of Nav1.8 currents and an attenuation of Nav1.7 currents. PKA-induced increase (Nav1.8) and decrease (Nav1.7) in peak currents were not associated with shifts in voltage-dependent activation or inactivation. The PKA-mediated increase in Nav1.8 current amplitude was prevented by chloroquine, suggesting that cell trafficking may contribute to the changes in Nav1.8 current amplitudes. A dose-dependent decrease in Nav1.7 and Nav1.8 currents was observed with the PKC activators PMA and PDBu. PMA induced shifts in the steady-state activation of Nav1.7 and Nav1.8 channels by 6.5 mV and 14 mV, respectively, in the depolarizing direction. The role of individual PKC isozymes in the regulation of Nav1.7 and Nav1.8 was determined using PKC-isozyme-specific peptide activators and inhibitors. The decrease in the Nav1.8 peak current induced by PMA was prevented by a specific 
PKC isozyme peptide antagonist, while the PMA effect on Nav1.7 was prevented by PKC and 
IIPKC peptide inhibitors. The data showed that Nav1.7 and Nav1.8 were differentially modulated by PKA and PKC. This is the first report demonstrating a functional role for PKC and IIPKC in the regulation of Nav1.7 and Nav1.8 Na+ channels. Identification of the particular PKC isozymes(s) that mediate the regulation of Na+ channels is essential for understanding the molecular mechanism involved in neuronal ion channel regulation in normal and pathological conditions.
This article has been cited by other articles:
|
|
 |
|
  A. Chatelier, L. Dahllund, A. Eriksson, J. Krupp, and M. Chahine Biophysical Properties of Human Nav1.7 Splice Variants and Their Regulation by Protein Kinase A J Neurophysiol, May 1, 2008; 99(5): 2241 - 2250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hudmon, J.-S. Choi, L. Tyrrell, J. A. Black, A. M. Rush, S. G. Waxman, and S. D. Dib-Hajj Phosphorylation of Sodium Channel Nav1.8 by p38 Mitogen-Activated Protein Kinase Increases Current Density in Dorsal Root Ganglion Neurons J. Neurosci., March 19, 2008; 28(12): 3190 - 3201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. De Col, K. Messlinger, and R. W. Carr Conduction velocity is regulated by sodium channel inactivation in unmyelinated axons innervating the rat cranial meninges J. Physiol., February 15, 2008; 586(4): 1089 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. R. Ostman, M. A. Nassar, J. N. Wood, and M. D. Baker GTP up-regulated persistent Na+ current and enhanced nociceptor excitability require NaV1.9 J. Physiol., February 15, 2008; 586(4): 1077 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. P. Few, T. Scheuer, and W. A. Catterall Dopamine modulation of neuronal Na+ channels requires binding of A kinase-anchoring protein 15and PKA by a modified leucine zipper motif PNAS, March 20, 2007; 104(12): 5187 - 5192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Amaya, H. Wang, M. Costigan, A. J. Allchorne, J. P. Hatcher, J. Egerton, T. Stean, V. Morisset, D. Grose, M. J. Gunthorpe, et al. The Voltage-Gated Sodium Channel Nav1.9 Is an Effector of Peripheral Inflammatory Pain Hypersensitivity J. Neurosci., December 13, 2006; 26(50): 12852 - 12860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Sheets, P. Gerner, C.-F. Wang, S.-Y. Wang, G. K. Wang, and T. R. Cummins Inhibition of Nav1.7 and Nav1.4 Sodium Channels by Trifluoperazine Involves the Local Anesthetic Receptor J Neurophysiol, October 1, 2006; 96(4): 1848 - 1859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Brackenbury and M. B. A. Djamgoz Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell line J. Physiol., June 1, 2006; 573(2): 343 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Lou, F. Laezza, B. R. Gerber, M. Xiao, K. A. Yamada, H. Hartmann, A. M. Craig, J. M. Nerbonne, and D. M. Ornitz Fibroblast growth factor 14 is an intracellular modulator of voltage-gated sodium channels J. Physiol., November 15, 2005; 569(1): 179 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Wittmack, A. M. Rush, A. Hudmon, S. G. Waxman, and S. D. Dib-Hajj Voltage-Gated Sodium Channel Nav1.6 Is Modulated by p38 Mitogen-Activated Protein Kinase J. Neurosci., July 13, 2005; 25(28): 6621 - 6630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Nassar, L. C. Stirling, G. Forlani, M. D. Baker, E. A. Matthews, A. H. Dickenson, and J. N. Wood Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain PNAS, August 24, 2004; 101(34): 12706 - 12711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Wittmack, A. M. Rush, M. J. Craner, M. Goldfarb, S. G. Waxman, and S. D. Dib-Hajj Fibroblast Growth Factor Homologous Factor 2B: Association with Nav1.6 and Selective Colocalization at Nodes of Ranvier of Dorsal Root Axons J. Neurosci., July 28, 2004; 24(30): 6765 - 6775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hong, T. J. Morrow, P. E. Paulson, L. L. Isom, and J. W. Wiley Early Painful Diabetic Neuropathy Is Associated with Differential Changes in Tetrodotoxin-sensitive and -resistant Sodium Channels in Dorsal Root Ganglion Neurons in the Rat J. Biol. Chem., July 9, 2004; 279(28): 29341 - 29350. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
