Ankyrin G and voltage gated sodium channels colocalize in human neuroma--key proteins of membrane remodeling after axonal injury.
We tested if ankyrin G could be detected in human neuroma, if it colocalized with site-specific peripheral nerve sodium channels that accumulate at axon tips of injured nerve, and if there are differences in the distribution of these proteins in non-painful neuroma and painful neuroma tissue vs. normal nerve. Frozen sections from one painful, six non-painful, and three normal nerves were immunocytochemically examined. A double labeling technique with highly specific antibodies against peripheral nerve type 1 (Na(v)1.7), and peripheral nerve type 3 (Na(v)1.8) sodium channels and anti-ankyrin G antibodies detected sodium channels and ankyrin G on the same section, using confocal laser scanning microscopy. Ankyrin G colocalized with both types of sodium channels. Neuroma specimens exhibited considerably larger immunofluorescence for both sodium channels and ankyrin G compared with normal nerve. The painful neuroma presented an even more pronounced immunolabeling in clusters. Findings support results from animal models that link ankyrin G with clustering of sodium channels at axon tips of unmyelinated, sprouting fibers. A common (repair-) mechanism that exists throughout the human nervous system for clustering sodium channels at a high density is assumed. A dysregulation in this membrane remodeling mechanism might be an initial step in a cascade that leads to a painful rather than a non-painful neuroma.
Kretschmer
Thomas
T
Department of Neurosurgery, University of Ulm, BKH Neurochirurgie, Ludwig-Heilmeyer-Strasse 2, D-89312 Günzburg, Germany. kretschmerthomas@hotmail.com
England
John D
JD
Happel
Leo T
LT
Liu
Z P
ZP
Thouron
Carol L
CL
Nguyen
Doan H
DH
Beuerman
Roger W
RW
Kline
David G
DG
D017487:Ankyrins / Q000032:analysis / Q000378:metabolism*; D001369:Axons / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009463:Neuroma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D009479:Neuropeptides / Q000032:analysis / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000032:analysis / Q000378:metabolism*
C490613:ANK3 protein, human; D017487:Ankyrins; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C568317:SCN10A protein, human; D015222:Sodium Channels