Ryanodine receptors contribute to the induction of nociceptive input-evoked long-term potentiation in the rat spinal cord slice.
BACKGROUND
Our previous study demonstrated that nitric oxide (NO) contributes to long-term potentiation (LTP) of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cord in vivo. Ryanodine receptor (RyR) is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway.


RESULTS
By means of field potential recordings in the adult male rat in vivo, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT) stably induced LTP of field excitatory postsynaptic potentials (fEPSPs). Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5)P3 receptor (IP(3)R) antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs). Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG) neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca(2+)]i in small DRG neurons.


CONCLUSIONS
These data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.
Cheng
Long-Zhen
LZ
Institute of Neurobiology, Institutes of Brain Science and State Key laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China. lzcheng@fudan.edu.cn
Lü
Ning
N
Zhang
Yu-Qiu
YQ
Zhao
Zhi-Qi
ZQ
D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002478:Cells, Cultured; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D019837:Ryanodine Receptor Calcium Release Channel; D009569:Nitric Oxide; D002110:Caffeine