FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon.
Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell's unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Navinactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials. In addition, leak conductance density along the distal axon is estimated as <1% that of somatodendritic membrane. The faster inactivation rate of FHF-free Navs together with very low axonal leak conductance serves to minimize ionic fluxes and energetic demand during repetitive spike conduction and at rest. The absence of FHFs from Navs at nodes of Ranvier in the central nervous system suggests a similar mechanism of current flux minimization along myelinated axons.
Department of Biological Sciences, Hunter College of City University, 695 Park Avenue, New York, New York 10065, USA.|Graduate Center of City University, Molecular, Cellular and Developmental Biology Subprogram, 365 Fifth Avenue, New York, New York 10016, USA.
Katarzyna
K
Dover
Department of Biological Sciences, Hunter College of City University, 695 Park Avenue, New York, New York 10065, USA.|Graduate Center of City University, Neuroscience Subprogram, 365 Fifth Avenue, New York, New York 10016, USA.
Christopher
C
Marra
Brain Connectivity Center, C. Mondino National Neurological Institute, Via Forlanini 6, Pavia 27100, Italy.
Sergio
S
Solinas
Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
Marko
M
Popovic
Department of Brain and Behavioral Science, University of Pavia, Via Forlanini 6, Pavia 27100, Italy.
Sathyaa
S
Subramaniyam
Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
Dejan
D
Zecevic
Brain Connectivity Center, C. Mondino National Neurological Institute, Via Forlanini 6, Pavia 27100, Italy.|Department of Brain and Behavioral Science, University of Pavia, Via Forlanini 6, Pavia 27100, Italy.
Egidio
E
D'Angelo
Department of Biological Sciences, Hunter College of City University, 695 Park Avenue, New York, New York 10065, USA.|Graduate Center of City University, Neuroscience Subprogram, 365 Fifth Avenue, New York, New York 10016, USA.
Mitchell
M
Goldfarb
J Neurosci. 2011 Jan 12;31(2):565-74
21228165
J Physiol. 2005 Nov 15;569(Pt 1):179-93
16166153
Proc Natl Acad Sci U S A. 1985 Feb;82(3):948-52
2579384
Neuron. 2007 Aug 2;55(3):449-63
17678857
Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12357-62
20566860
Front Cell Neurosci. 2015 Jun 04;9:205
26089778
J Physiol. 2010 Oct 1;588(Pt 19):3695-711
20679355
Science. 2015 Dec 11;350(6266):1361-6
26586188
Cell. 2009 Mar 20;136(6):1148-60
19268344
J Neurosci. 2004 Jul 28;24(30):6765-75
15282281
Structure. 2012 Jul 3;20(7):1167-76
22705208
J Neurosci. 1999 Sep 1;19(17):7516-28
10460258
Nat Methods. 2014 Aug;11(8):825-33
24952910
J Physiol. 1995 Apr 15;484 ( Pt 2):397-413
7602534
J Neurosci. 1996 Nov 1;16(21):6676-86
8824308
Neuron. 1995 Sep;15(3):637-47
7546743
PLoS Comput Biol. 2010 Jul 01;6:e1000840
20617202
J Cereb Blood Flow Metab. 2012 Jul;32(7):1222-32
22434069
Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4051-6
23341597
J Neurosci. 2014 Nov 26;34(48):16126-39
25429153
Mol Cell Neurosci. 2009 Oct;42(2):90-101
19465131
J Biol Chem. 2009 Jun 26;284(26):17883-96
19406745
J Neurophysiol. 2009 Feb;101(2):519-32
19073816
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):13014-7
7809165
J Neurosci. 2015 Apr 29;35(17):6752-69
25926453
J Cell Biol. 2014 Apr 14;205(1):67-81
24711503
Biophys J. 1987 Dec;52(6):1087-90
2447971
J Physiol. 2004 Feb 1;554(Pt 3):829-39
14634204
Eur J Neurosci. 2006 May;23(10):2551-62
16817858
J Neurosci. 2004 Jul 28;24(30):6703-14
15282273
Mol Cell Neurosci. 2013 Sep;56:393-403
23891806
J Neurosci. 2003 Jun 15;23(12):4899-912
12832512
J Neurophysiol. 2012 Jun;107(11):2958-70
22378171
J Neurosci. 2000 Dec 15;20(24):9162-73
11124994
J Neurosci. 2013 Oct 23;33(43):16924-9
24155298
J Neurosci. 1998 Jan 1;18(1):36-47
9412484
J Neurosci. 2001 Sep 1;21(17):6666-72
11517256
Curr Biol. 2001 May 15;11(10):793-7
11378392