Gabapentin selectively reduces persistent sodium current in injured type-A dorsal root ganglion neurons.
It has been confirmed that the voltage-gated persistent sodium currents mediate the generation of subthreshold membrane potential oscillations (SMPOs) and contribute to shaping repetitive firing. Our previous study indicated that gabapentin (GBP) administration induced a dose-dependent inhibition of SMPO in chronically compressed dorsal root ganglion (CCD) neurons. To investigate the mechanisms and possible site(s) of action of GBP, the persistent sodium currents (I(NaP)) were measured and the effects of GBP on I(NaP) were examined in CCD neurons electrophysiologically in vitro. DRG neurons possess slow TTX-sensitive inactivating sodium currents that significantly contribute to the generation of membrane oscillations by amplifying the resonance behavior. GBP reduced the resonant amplitude of DRG neurons as well as inhibiting the firing and SMPO induced by injection current, which was strongly due to the inhibitory effect on persistent sodium currents. Furthermore, we found that GBP (1-20 microM) administration inhibited the persistent sodium currents in dose-dependent manner, while the changes of K(+) and Ca(2+) current minimally contributed to the effect of GBP on oscillation and resonant behavior of DRG neurons. In contrast, the amplitude and voltage-dependence of transient sodium current were unchanged by GBP. The results suggest that GBP decreased the amplitude of resonance and abolished the SMPO of A-type DRG neurons through the inhibition of I(NaP), and thus inhibited the SMPO dependent repetitive and bursting firings.
Yang
Rui-Hua
RH
epartment of Occupational and Environmental Health, The Fourth Military Medical University, Xi'an 710032, PR China. sjhu@fmmu.edu.cn
Wang
Wen-Ting
WT
Chen
Jing-Yuan
JY
Xie
Rou-Gang
RG
Hu
San-Jue
SJ
D000588:Amines / Q000008:administration & dosage*; D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D000077206:Gabapentin; D005727:Ganglia, Spinal / Q000187:drug effects / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009408:Nerve Compression Syndromes / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D015222:Sodium Channels; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D012964:Sodium