| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Neurobiology and Physiology, Northwestern University, Evanston 60208; and 2Department of Physiology, Northwestern University Medical School, Chicago, Illinois 60611
Submitted 17 March 2004; accepted in final form 19 June 2004
Action potential firing rates are generally limited by the refractory period, which depends on the recovery from inactivation of voltage-gated Na channels. In cerebellar Purkinje neurons, the kinetics of Na channels appear specialized for rapid firing. Upon depolarization, an endogenous open-channel blocker rapidly terminates current flow but prevents binding of the "fast" inactivation gate. Upon repolarization, unbinding of the blocker produces "resurgent" Na current while allowing channels to recover rapidly. Because other cerebellar neurons, including granule cells, unipolar brush cells, and neurons of the cerebellar nuclei, also fire rapidly, we tested whether these cells might also express Na channels with resurgent kinetics. Neurons were acutely isolated from mice and rats, and TTX-sensitive Na currents were recorded under voltage clamp. Unlike Purkinje cells, the other cerebellar neurons produced only tiny resurgent currents in solutions optimized for voltage-clamping Na currents (50 mM Na+; Co2+ substitution for Ca2+). Under more physiological ionic conditions (155 mM Na+; 2 mM Ca2+ with 0.03 mM Cd2+), however, granule cells, unipolar brush cells, and cerebellar nuclear cells all produced robust resurgent currents. The increase in resurgent current, which was greater than predicted by the Goldman-Hodgkin-Katz equation, appeared to result from a combination of knock-off of open-channel blockers by permeating ions as well as relief of divalent block at negative potentials. These results indicate that resurgent current is typical of many cerebellar neurons and suggest that rapid open-channel block and unblock may be a widespread mechanism for restoration of Na channel availability in rapidly firing neurons.
This article has been cited by other articles:
|
|
 |
|
  N. Zheng and I. M. Raman Ca Currents Activated by Spontaneous Firing and Synaptic Disinhibition in Neurons of the Cerebellar Nuclei J. Neurosci., August 5, 2009; 29(31): 9826 - 9838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Aman, T. M. Grieco-Calub, C. Chen, R. Rusconi, E. A. Slat, L. L. Isom, and I. M. Raman Regulation of Persistent Na Current by Interactions between {beta} Subunits of Voltage-Gated Na Channels J. Neurosci., February 18, 2009; 29(7): 2027 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Molineux, W. H. Mehaffey, R. Tadayonnejad, D. Anderson, A. F. Tennent, and R. W. Turner Ionic Factors Governing Rebound Burst Phenotype in Rat Deep Cerebellar Neurons J Neurophysiol, November 1, 2008; 100(5): 2684 - 2701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Gittis and S. du Lac Similar Properties of Transient, Persistent, and Resurgent Na Currents in GABAergic and Non-GABAergic Vestibular Nucleus Neurons J Neurophysiol, May 1, 2008; 99(5): 2060 - 2065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Mercer, C. S. Chan, T. Tkatch, J. Held, and D. J. Surmeier Nav1.6 Sodium Channels Are Critical to Pacemaking and Fast Spiking in Globus Pallidus Neurons J. Neurosci., December 5, 2007; 27(49): 13552 - 13566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Kalume, F. H. Yu, R. E. Westenbroek, T. Scheuer, and W. A. Catterall Reduced Sodium Current in Purkinje Neurons from NaV1.1 Mutant Mice: Implications for Ataxia in Severe Myoclonic Epilepsy in Infancy J. Neurosci., October 10, 2007; 27(41): 11065 - 11074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Yool Aquaporins: Multiple Roles in the Central Nervous System Neuroscientist, October 1, 2007; 13(5): 470 - 485. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Castelli, G. Biella, M. Toselli, and J. Magistretti Resurgent Na+ current in pyramidal neurones of rat perirhinal cortex: axonal location of channels and contribution to depolarizing drive during repetitive firing J. Physiol., August 1, 2007; 582(3): 1179 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Russo, E. Mugnaini, and M. Martina Intrinsic properties and mechanisms of spontaneous firing in mouse cerebellar unipolar brush cells J. Physiol., June 1, 2007; 581(2): 709 - 724. [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]
|
|
|
|
|
|
M. Uusisaari, K. Obata, and T. Knopfel Morphological and Electrophysiological Properties of GABAergic and Non-GABAergic Cells in the Deep Cerebellar Nuclei J Neurophysiol, January 1, 2007; 97(1): 901 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. I. Levin, Z. M. Khaliq, T. K. Aman, T. M. Grieco, J. A. Kearney, I. M. Raman, and M. H. Meisler Impaired Motor Function in Mice With Cell-Specific Knockout of Sodium Channel Scn8a (NaV1.6) in Cerebellar Purkinje Neurons and Granule Cells J Neurophysiol, August 1, 2006; 96(2): 785 - 793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. de Ruiter, C. I. De Zeeuw, and C. Hansel Voltage-Gated Sodium Channels in Cerebellar Purkinje Cells of Mormyrid Fish J Neurophysiol, July 1, 2006; 96(1): 378 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Magistretti, L. Castelli, L. Forti, and E. D'Angelo Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study J. Physiol., May 15, 2006; 573(1): 83 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sekirnjak and S. du Lac Physiological and Anatomical Properties of Mouse Medial Vestibular Nucleus Neurons Projecting to the Oculomotor Nucleus J Neurophysiol, May 1, 2006; 95(5): 3012 - 3023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Wang, T. Edrich, and S.-Y. Wang Time-Dependent Block and Resurgent Tail Currents Induced by Mouse {beta}4154-167 Peptide in Cardiac Na+ Channels J. Gen. Physiol., February 27, 2006; 127(3): 277 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Ulbricht Sodium Channel Inactivation: Molecular Determinants and Modulation Physiol Rev, October 1, 2005; 85(4): 1271 - 1301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ptak, G. G. Zummo, G. F. Alheid, T. Tkatch, D. J. Surmeier, and D. R. McCrimmon Sodium Currents in Medullary Neurons Isolated from the Pre-Botzinger Complex Region J. Neurosci., May 25, 2005; 25(21): 5159 - 5170. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
