Sialic acid contributes to hyperexcitability of dorsal root ganglion neurons in rats with peripheral nerve injury.
Axonal injury of the dorsal root ganglion (DRG) neurons may alter the synthesis of certain membrane proteins that are responsible for the development of abnormal hyperexcitability. The external domains of most of these membrane proteins are sialylated. Because sialic acid carries heavy negative charges, the increase of sialylated proteins may increase neurons' negative surface charges, which will have predictable effects on the voltage-gated channels, and affect the excitability of injured neurons. Using intracellular electrophysiological recording, we demonstrated that following chronic constriction injury (CCI) of the sciatic nerve, Aalpha/beta DRG neurons become hyperexcitable, as indicated by a more depolarized resting membrane potential (Vm) and a lowered threshold current (TIC). More interestingly, the excitability of injured DRG neurons was reduced substantially when the extracellular sialic acid was removed by pretreatment with neuraminidase. The Vm was less depolarized and the TIC increased robustly as compared to the CCI neurons without neuraminidase treatment. However, desialylation of normal, intact neurons had no significant effect on the Vm and less effect on the TIC. Our results suggest that the hyperexcitability of injured sensory neurons may be associated with increased negatively charged sialic acid residues on the surface of the neuronal somata.
Peng
Xiao-Qing
XQ
Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, #5 Dong Dan San Tiao, Beijing 100005, China. xpeng@intra.nida.nih.gov
Zhang
Xiu-Lin
XL
Fang
Yan
Y
Xie
Wen-Rui
WR
Xie
Yi-Kuan
YK
D000818:Animals; D003250:Constriction; D004558:Electric Stimulation / Q000379:methods; D005727:Ganglia, Spinal / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology*; D009431:Neural Conduction / Q000187:drug effects / Q000528:radiation effects; D009439:Neuraminidase / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000473:pathology*; D051381:Rats
D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid