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Differential action potentials and firing patterns in injured and uninjured small dorsal root ganglion neurons after nerve injury.
Brain Res. 2004 May 29; 1009(1-2):147-58.BR

Abstract

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.

Authors+Show Affiliations

Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. xufeng.zhang@abbott.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15120592

Citation

Zhang, Xu-Feng, et al. "Differential Action Potentials and Firing Patterns in Injured and Uninjured Small Dorsal Root Ganglion Neurons After Nerve Injury." Brain Research, vol. 1009, no. 1-2, 2004, pp. 147-58.
Zhang XF, Zhu CZ, Thimmapaya R, et al. Differential action potentials and firing patterns in injured and uninjured small dorsal root ganglion neurons after nerve injury. Brain Res. 2004;1009(1-2):147-58.
Zhang, X. F., Zhu, C. Z., Thimmapaya, R., Choi, W. S., Honore, P., Scott, V. E., Kroeger, P. E., Sullivan, J. P., Faltynek, C. R., Gopalakrishnan, M., & Shieh, C. C. (2004). Differential action potentials and firing patterns in injured and uninjured small dorsal root ganglion neurons after nerve injury. Brain Research, 1009(1-2), 147-58.
Zhang XF, et al. Differential Action Potentials and Firing Patterns in Injured and Uninjured Small Dorsal Root Ganglion Neurons After Nerve Injury. Brain Res. 2004 May 29;1009(1-2):147-58. PubMed PMID: 15120592.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential action potentials and firing patterns in injured and uninjured small dorsal root ganglion neurons after nerve injury. AU - Zhang,Xu-Feng, AU - Zhu,Chang Z, AU - Thimmapaya,Rama, AU - Choi,Won S, AU - Honore,Prisca, AU - Scott,Victoria E, AU - Kroeger,Paul E, AU - Sullivan,James P, AU - Faltynek,Connie R, AU - Gopalakrishnan,Murali, AU - Shieh,Char-Chang, PY - 2004/02/21/accepted PY - 2004/5/4/pubmed PY - 2004/7/13/medline PY - 2004/5/4/entrez SP - 147 EP - 58 JF - Brain research JO - Brain Res VL - 1009 IS - 1-2 N2 - 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. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/15120592/Differential_action_potentials_and_firing_patterns_in_injured_and_uninjured_small_dorsal_root_ganglion_neurons_after_nerve_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006899304003981 DB - PRIME DP - Unbound Medicine ER -