Differential action potentials and firing patterns in injured and uninjured small dorsal root ganglion neurons after nerve injury.
The profile of tetrodotoxin sensitive (TTX-S) and resistant (TTX-R) Na(+) channels and their contribution to action potentials and firing patterns were studied in isolated small dorsal root ganglion (DRG) neurons after L5/L6 spinal nerve ligation (SNL). Total TTX-R Na(+) currents and Na(v) 1.8 mRNA were reduced in injured L5 DRG neurons 14 days after SNL. In contrast, TTX-R Na(+)currents and Na(v) 1.8 mRNA were upregulated in uninjured L4 DRG neurons after SNL. Voltage-dependent inactivation of TTX-R Na(+) channels in these neurons was shifted to hyperpolarized potentials by 4 mV. Two types of neurons were identified in injured L5 DRG neurons after SNL. Type I neurons (57%) had significantly lower threshold but exhibited normal resting membrane potential (RMP) and action potential amplitude. Type II neurons (43%) had significantly smaller action potential amplitude but retained similar RMP and threshold to those from sham rats. None of the injured neurons could generate repetitive firing. In the presence of TTX, only 26% of injured neurons could generate action potentials that had smaller amplitude, higher threshold, and higher rheobase compared with sham rats. In contrast, action potentials and firing patterns in uninjured L4 DRG neurons after SNL, in the presence or absence of TTX, were not affected. These results suggest that TTX-R Na(+) channels play important roles in regulating action potentials and firing patterns in small DRG neurons and that downregulation in injured neurons and upregulation in uninjured neurons confer differential roles in shaping electrogenesis, and perhaps pain transmission, in these neurons.
Zhang
Xu-Feng
XF
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. xufeng.zhang@abbott.com
Zhu
Chang Z
CZ
Thimmapaya
Rama
R
Choi
Won S
WS
Honore
Prisca
P
Scott
Victoria E
VE
Kroeger
Paul E
PE
Sullivan
James P
JP
Faltynek
Connie R
CR
Gopalakrishnan
Murali
M
Shieh
Char-Chang
CC
D000200:Action Potentials / Q000502:physiology*; D000578:Amidines; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000166:cytology* / Q000293:injuries; D005786:Gene Expression Regulation; D015640:Ion Channel Gating; D008026:Ligation / Q000379:methods; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009475:Neurons, Afferent / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement; D018408:Patch-Clamp Techniques / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012584:Sciatic Nerve / Q000502:physiology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries* / Q000503:physiopathology*; D013779:Tetrodotoxin / Q000494:pharmacology
D000578:Amidines; D000779:Anesthetics, Local; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C568319:Scn10a protein, rat; D015222:Sodium Channels; C031455:diamidino compound 253-50; D013779:Tetrodotoxin