 |
||||
|
||||
|
||||
|
||||
.gif?ad=17923&adview=true)
Previous Article | Next Article
The Journal of Neuroscience, December 1, 1998, 18(23):9607-9619
Slow Closed-State Inactivation: A Novel Mechanism Underlying Ramp Currents in Cells Expressing the hNE/PN1 Sodium Channel
Theodore R. Cummins1, 3, James R. Howe2, and Stephen G. Waxman1, 2, 3 Departments of 1 Neurology and 2 Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510, and 3 Neuroscience Research Center, Veterans Administration Medical Center, West Haven, Connecticut 06516
To better understand why sensory neurons express voltage-gated Na+ channel isoforms that are different from those expressed in other types of excitable cells, we compared the properties of the hNE sodium channel [a human homolog of PN1, which is selectively expressed in dorsal root ganglion (DRG) neurons] with that of the skeletal muscle Na+ channel (hSkM1) [both expressed in human embryonic kidney (HEK293) cells]. Although the voltage dependence of activation was similar, the inactivation properties were different. The V1/2 for steady-state inactivation was slightly more negative, and the rate of open-state inactivation was ~50% slower for hNE. However, the greatest difference was that closed-state inactivation and recovery from inactivation were up to fivefold slower for hNE than for hSkM1 channels. TTX-sensitive (TTX-S) currents in small DRG neurons also have slow closed-state inactivation, suggesting that hNE/PN1 contributes to this TTX-S current. Slow ramp depolarizations (0.25 mV/msec) elicited TTX-S persistent currents in cells expressing hNE channels, and in DRG neurons, but not in cells expressing hSkM1 channels. We propose that slow closed-state inactivation underlies these ramp currents. This conclusion is supported by data showing that divalent cations such as Cd2+ and Zn2+ (50-200 µM) slowed closed-state inactivation and also dramatically increased the ramp currents for DRG TTX-S currents and hNE channels but not for hSkM1 channels. The hNE and DRG TTX-S ramp currents activated near
65 mV and therefore could play an important role in boosting stimulus depolarizations in sensory neurons. These results suggest that differences in the kinetics of closed-state inactivation may confer distinct integrative properties on different Na+ channel isoforms.
Key words: sodium channel; persistent current; dorsal root ganglion; excitability; tetrodotoxin; expression
Copyright © 1998 Society for Neuroscience 0270-6474/98/18239607-13$05.00/0
This article has been cited by other articles:
P. L. Sheets, C. Heers, T. Stoehr, and T. R. Cummins
Differential Block of Sensory Neuronal Voltage-Gated Sodium Channels by Lacosamide [(2R)-2-(Acetylamino)-N-benzyl-3-methoxypropanamide], Lidocaine, and Carbamazepine
J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 89 - 99.
[Abstract] [Full Text] [PDF]
K. P. Carlin, J. Liu, and L. M. Jordan
Postnatal Changes in the Inactivation Properties of Voltage-Gated Sodium Channels Contribute to the Mature Firing Pattern of Spinal Motoneurons
J Neurophysiol, June 1, 2008; 99(6): 2864 - 2876.
[Abstract] [Full Text] [PDF]
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]
R. L. Ruff
Upsetting the balance among membrane channels can produce hyperexcitability or inexcitability
Neurology, November 27, 2007; 69(22): 2036 - 2037.
[Full Text] [PDF]
P. L. Sheets, J. O. Jackson II, S. G. Waxman, S. D. Dib-Hajj, and T. R. Cummins
A Nav1.7 channel mutation associated with hereditary erythromelalgia contributes to neuronal hyperexcitability and displays reduced lidocaine sensitivity
J. Physiol., June 15, 2007; 581(3): 1019 - 1031.
[Abstract] [Full Text] [PDF]
J. J. Smith, T. R. Cummins, S. Alphy, and K. M. Blumenthal
Molecular Interactions of the Gating Modifier Toxin ProTx-II with Nav1.5: IMPLIED EXISTENCE OF A NOVEL TOXIN BINDING SITE COUPLED TO ACTIVATION
J. Biol. Chem., April 27, 2007; 282(17): 12687 - 12697.
[Abstract] [Full Text] [PDF]
A. M. Rush, T. R. Cummins, and S. G. Waxman
Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons
J. Physiol., February 15, 2007; 579(1): 1 - 14.
[Abstract] [Full Text] [PDF]
J. R. A. Wooltorton, S. Gaboyard, K. M. Hurley, S. D. Price, J. L. Garcia, M. Zhong, A. Lysakowski, and R. A. Eatock
Developmental Changes in Two Voltage-Dependent Sodium Currents in Utricular Hair Cells
J Neurophysiol, February 1, 2007; 97(2): 1684 - 1704.
[Abstract] [Full Text] [PDF]
T. P. Harty, S. D. Dib-Hajj, L. Tyrrell, R. Blackman, F. M. Hisama, J. B. Rose, and S. G. Waxman
Nav1.7 Mutant A863P in Erythromelalgia: Effects of Altered Activation and Steady-State Inactivation on Excitability of Nociceptive Dorsal Root Ganglion Neurons
J. Neurosci., November 29, 2006; 26(48): 12566 - 12575.
[Abstract] [Full Text] [PDF]
A. Lampert, S. D. Dib-Hajj, L. Tyrrell, and S. G. Waxman
Size Matters: Erythromelalgia Mutation S241T in Nav1.7 Alters Channel Gating
J. Biol. Chem., November 24, 2006; 281(47): 36029 - 36035.
[Abstract] [Full Text] [PDF]
A. M. Rush, S. D. Dib-Hajj, S. Liu, T. R. Cummins, J. A. Black, and S. G. Waxman
A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons
PNAS, May 23, 2006; 103(21): 8245 - 8250.
[Abstract] [Full Text] [PDF]
S. D. Dib-Hajj, A. M. Rush, T. R. Cummins, F. M. Hisama, S. Novella, L. Tyrrell, L. Marshall, and S. G. Waxman
Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons
Brain, August 1, 2005; 128(8): 1847 - 1854.
[Abstract] [Full Text] [PDF]
A. M. Rush, S. D. Dib-Hajj, and S. G. Waxman
Electrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones
J. Physiol., May 1, 2005; 564(3): 803 - 815.
[Abstract] [Full Text] [PDF]
M. M. McNulty and D. A. Hanck
State-Dependent Mibefradil Block of Na+ Channels
Mol. Pharmacol., December 1, 2004; 66(6): 1652 - 1661.
[Abstract] [Full Text] [PDF]
T. R. Cummins, S. D. Dib-Hajj, and S. G. Waxman
Electrophysiological Properties of Mutant Nav1.7 Sodium Channels in a Painful Inherited Neuropathy
J. Neurosci., September 22, 2004; 24(38): 8232 - 8236.
[Abstract] [Full Text] [PDF]
A. Agoston, L. Kunz, A. Krieger, and A. Mayerhofer
Two Types of Calcium Channels in Human Ovarian Endocrine Cells: Involvement in Steroidogenesis
J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4503 - 4512.
[Abstract] [Full Text] [PDF]
J. F. Hoffman, A. Dodson, A. Wickrema, and S. D. Dib-Hajj
Tetrodotoxin-sensitive Na+ channels and muscarinic and purinergic receptors identified in human erythroid progenitor cells and red blood cell ghosts
PNAS, August 17, 2004; 101(33): 12370 - 12374.
[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]
R. I. Herzog, C. Liu, S. G. Waxman, and T. R. Cummins
Calmodulin Binds to the C Terminus of Sodium Channels Nav1.4 and Nav1.6 and Differentially Modulates Their Functional Properties
J. Neurosci., September 10, 2003; 23(23): 8261 - 8270.
[Abstract] [Full Text] [PDF]
T.R. Cummins, M. Renganathan, P.K. Stys, R.I. Herzog, K. Scarfo, R. Horn, S.D. Dib-Hajj, and S.G. Waxman
The pentapeptide QYNAD does not block voltage-gated sodium channels
Neurology, January 28, 2003; 60(2): 224 - 229.
[Abstract] [Full Text] [PDF]
T. R. Cummins, S. D. Dib-Hajj, S. G. Waxman, and D. F. Donnelly
Characterization and Developmental Changes of Na+ Currents of Petrosal Neurons With Projections to the Carotid Body
J Neurophysiol, December 1, 2002; 88(6): 2993 - 3002.
[Abstract] [Full Text] [PDF]
A. Leffler, T. R. Cummins, S. D. Dib-Hajj, W. N. Hormuzdiar, J. A. Black, and S. G. Waxman
GDNF and NGF Reverse Changes in Repriming of TTX-Sensitive Na+ Currents Following Axotomy of Dorsal Root Ganglion Neurons
J Neurophysiol, August 1, 2002; 88(2): 650 - 658.
[Abstract] [Full Text] [PDF]
T. R. Cummins, F. Aglieco, and S. D. Dib-Hajj
Critical Molecular Determinants of Voltage-Gated Sodium Channel Sensitivity to {micro}-Conotoxins GIIIA/B
Mol. Pharmacol., May 1, 2002; 61(5): 1192 - 1201.
[Abstract] [Full Text] [PDF]
T. R. Cummins, F. Aglieco, M. Renganathan, R. I. Herzog, S. D. Dib-Hajj, and S. G. Waxman
Nav1.3 Sodium Channels: Rapid Repriming and Slow Closed-State Inactivation Display Quantitative Differences after Expression in a Mammalian Cell Line and in Spinal Sensory Neurons
J. Neurosci., August 15, 2001; 21(16): 5952 - 5961.
[Abstract] [Full Text] [PDF]
S. C. Benn, M. Costigan, S. Tate, M. Fitzgerald, and C. J. Woolf
Developmental Expression of the TTX-Resistant Voltage-Gated Sodium Channels Nav1.8 (SNS) and Nav1.9 (SNS2) in Primary Sensory Neurons
J. Neurosci., August 15, 2001; 21(16): 6077 - 6085.
[Abstract] [Full Text] [PDF]
M. Renganathan, T. R. Cummins, and S. G. Waxman
Contribution of Nav1.8 Sodium Channels to Action Potential Electrogenesis in DRG Neurons
J Neurophysiol, August 1, 2001; 86(2): 629 - 640.
[Abstract] [Full Text] [PDF]
M. Renganathan, T. R. Cummins, W. N. Hormuzdiar, and S. G. Waxman
alpha -SNS Produces the Slow TTX-Resistant Sodium Current in Large Cutaneous Afferent DRG Neurons
J Neurophysiol, August 1, 2000; 84(2): 710 - 718.
[Abstract] [Full Text] [PDF]
N. A. Gorelova and C. R. Yang
Dopamine D1/D5 Receptor Activation Modulates a Persistent Sodium Current in Rat Prefrontal Cortical Neurons In Vitro
J Neurophysiol, July 1, 2000; 84(1): 75 - 87.
[Abstract] [Full Text] [PDF]
J. Magistretti, D. S. Ragsdale, and A. Alonso
High Conductance Sustained Single-Channel Activity Responsible for the Low-Threshold Persistent Na+ Current in Entorhinal Cortex Neurons
J. Neurosci., September 1, 1999; 19(17): 7334 - 7341.
[Abstract] [Full Text] [PDF]
M. D. Bevan and C. J. Wilson
Mechanisms Underlying Spontaneous Oscillation and Rhythmic Firing in Rat Subthalamic Neurons
J. Neurosci., September 1, 1999; 19(17): 7617 - 7628.
[Abstract] [Full Text] [PDF]
S. G. Waxman, S. Dib-Hajj, T. R. Cummins, and J. A. Black
Sodium channels and pain
PNAS, July 6, 1999; 96(14): 7635 - 7639.
[Abstract] [Full Text] [PDF]
M. Tanaka, T. R. Cummins, K. Ishikawa, J. A. Black, Y. Ibata, and S. G. Waxman
Molecular and functional remodeling of electrogenic membrane of hypothalamic neurons in response to changes in their input
PNAS, February 2, 1999; 96(3): 1088 - 1093.
[Abstract] [Full Text] [PDF]
J. Fjell, T. R. Cummins, K. Fried, J. A. Black, and S. G. Waxman
In Vivo NGF Deprivation Reduces SNS Expression and TTX-R Sodium Currents in IB4-Negative DRG Neurons
J Neurophysiol, February 1, 1999; 81(2): 803 - 810.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|