 |
The Journal of Neuroscience, February 15, 2006, 26(7):1935-1944; doi:10.1523/JNEUROSCI.4664-05.2006
 Previous Article | Next Article 
Cellular/Molecular
Relative Contributions of Axonal and Somatic Na Channels to Action Potential Initiation in Cerebellar Purkinje Neurons
Zayd M. Khaliq and
Indira M. Raman
Department of Neurobiology and Physiology and Institute for Neuroscience, Northwestern University, Evanston, Illinois 60208
Correspondence should be addressed to Indira M. Raman, Department of Neurobiology and Physiology, 2205 Tech Drive, Northwestern University, Evanston, IL 60208. Email: i-raman{at}northwestern.edu
Neuronal excitability is likely to be regulated by the site of action potential initiation, the location on a neuron that crosses threshold first. Although initiation is axonal in many neurons, in Purkinje cells, somatic conductances can generate spontaneous action potentials, suggesting that the perisomatic region (soma and/or initial segment) contributes to spike initiation and may regulate firing. To identify directly the cellular regions at which Na channel modulation significantly influences firing, we measured spontaneous and evoked action potentials in Purkinje cells in cerebellar slices from postnatal day 14–28 mice while applying drugs locally to either the soma/initial segment or the first node of Ranvier. Na currents were decreased by tetrodotoxin (TTX) or increased by  -pompilidotoxin (-PMTX). Dual somatic and axonal recordings indicated that spike thresholds and input–output curves were sensitive to TTX or -PMTX at the perisomatic region but were unchanged by either drug at the first node. When perisomatic Na channel availability was reduced with subsaturating TTX, however, the input–output curve became shallower during additional TTX block of nodal channels, revealing a latent role for nodal Na channels in facilitating firing. In perisomatic TTX, axons failed to generate spontaneous or evoked spike trains. In contrast, choline block of the initial segment alone altered normal input–output curves. The data suggest that, although the first node reliably follows action potentials, spike initiation in Purkinje neurons occurs in the initial segment. Moreover, Purkinje cell output depends on the density, availability, and kinetics of perisomatic Na channels, a characteristic that may distinguish spontaneously firing from quiescent neurons.
Key words: axon; initial segment; propagation; node of Ranvier; resurgent; Na current
Received Nov. 1, 2005;
revised Jan. 3, 2006;
accepted Jan. 3, 2006.
Correspondence should be addressed to Indira M. Raman, Department of Neurobiology and Physiology, 2205 Tech Drive, Northwestern University, Evanston, IL 60208. Email: i-raman{at}northwestern.edu
This article has been cited by other articles:
|
|
|
|
 
M. Royeck, M.-T. Horstmann, S. Remy, M. Reitze, Y. Yaari, and H. Beck
Role of Axonal NaV1.6 Sodium Channels in Action Potential Initiation of CA1 Pyramidal Neurons
J Neurophysiol,
October 1, 2008;
100(4):
2361 - 2380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. W. Wu, C. S. Chan, D. J. Surmeier, and J. F. Disterhoft
Coupling of L-Type Ca2+ Channels to KV7/KCNQ Channels Creates a Novel, Activity-Dependent, Homeostatic Intrinsic Plasticity
J Neurophysiol,
October 1, 2008;
100(4):
1897 - 1908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Idoux, D. Eugene, A. Chambaz, C. Magnani, J. A. White, and L. E. Moore
Control of Neuronal Persistent Activity by Voltage-Dependent Dendritic Properties
J Neurophysiol,
September 1, 2008;
100(3):
1278 - 1286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. T. Davie, B. A. Clark, and M. Hausser
The Origin of the Complex Spike in Cerebellar Purkinje Cells
J. Neurosci.,
July 23, 2008;
28(30):
7599 - 7609.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Kress, M. J. Dowling, J. P. Meeks, and S. Mennerick
High Threshold, Proximal Initiation, and Slow Conduction Velocity of Action Potentials in Dentate Granule Neuron Mossy Fibers
J Neurophysiol,
July 1, 2008;
100(1):
281 - 291.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ogawa, I. Horresh, J. S. Trimmer, D. S. Bredt, E. Peles, and M. N. Rasband
Postsynaptic Density-93 Clusters Kv1 Channels at Axon Initial Segments Independently of Caspr2
J. Neurosci.,
May 28, 2008;
28(22):
5731 - 5739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Susuki and M. N. Rasband
Spectrin and Ankyrin-Based Cytoskeletons at Polarized Domains in Myelinated Axons
Experimental Biology and Medicine,
April 1, 2008;
233(4):
394 - 400.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Sjostrom, E. A. Rancz, A. Roth, and M. Hausser
Dendritic Excitability and Synaptic Plasticity
Physiol Rev,
April 1, 2008;
88(2):
769 - 840.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Schmidt-Hieber, P. Jonas, and J. Bischofberger
Action potential initiation and propagation in hippocampal mossy fibre axons
J. Physiol.,
April 1, 2008;
586(7):
1849 - 1857.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. X. Zhang and L. L. Thio
Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons
J Neurophysiol,
December 1, 2007;
98(6):
3666 - 3676.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Laezza, B. R. Gerber, J.-Y. Lou, M. A. Kozel, H. Hartman, A. Marie Craig, D. M. Ornitz, and J. M. Nerbonne
The FGF14F145S Mutation Disrupts the Interaction of FGF14 with Voltage-Gated Na+ Channels and Impairs Neuronal Excitability
J. Neurosci.,
October 31, 2007;
27(44):
12033 - 12044.
[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]
|
|
|
|
|
|
|
L. L. Scott, T. A. Hage, and N. L. Golding
Weak action potential backpropagation is associated with high-frequency axonal firing capability in principal neurons of the gerbil medial superior olive
J. Physiol.,
September 1, 2007;
583(2):
647 - 661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. Hedstrom, X. Xu, Y. Ogawa, R. Frischknecht, C. I. Seidenbecher, P. Shrager, and M. N. Rasband
Neurofascin assembles a specialized extracellular matrix at the axon initial segment
J. Cell Biol.,
August 27, 2007;
178(5):
875 - 886.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Meeks and S. Mennerick
Action Potential Initiation and Propagation in CA3 Pyramidal Axons
J Neurophysiol,
May 1, 2007;
97(5):
3460 - 3472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. N. Blythe, J. F. Atherton, and M. D. Bevan
Synaptic Activation of Dendritic AMPA and NMDA Receptors Generates Transient High-Frequency Firing in Substantia Nigra Dopamine Neurons In Vitro
J Neurophysiol,
April 1, 2007;
97(4):
2837 - 2850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. K. Aman and I. M. Raman
Subunit Dependence of Na Channel Slow Inactivation and Open Channel Block in Cerebellar Neurons
Biophys. J.,
March 15, 2007;
92(6):
1938 - 1951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Ashida, K. Abe, K. Funabiki, and M. Konishi
Passive Soma Facilitates Submillisecond Coincidence Detection in the Owl's Auditory System
J Neurophysiol,
March 1, 2007;
97(3):
2267 - 2282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yang, Y. Ogawa, K. L. Hedstrom, and M. N. Rasband
{beta}IV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG
J. Cell Biol.,
February 12, 2007;
176(4):
509 - 519.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Boiko, M. Vakulenko, H. Ewers, C. C. Yap, C. Norden, and B. Winckler
Ankyrin-Dependent and -Independent Mechanisms Orchestrate Axonal Compartmentalization of L1 Family Members Neurofascin and L1/Neuron-Glia Cell Adhesion Molecule
J. Neurosci.,
January 17, 2007;
27(3):
590 - 603.
[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]
|
|
|
|
