Effect of resiniferatoxin on glutamatergic spontaneous excitatory synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord.
The transient receptor potential (TRP) vanilloid type 1 (TRPV1) agonist, capsaicin, enhances glutamatergic spontaneous excitatory synaptic transmission in CNS neurons. Resiniferatoxin (RTX) has a much higher affinity for TRPV1 than capsaicin, but its ability to modulate excitatory transmission is unclear. We examined the effect of RTX on excitatory transmission using the whole-cell patch-clamp technique in substantia gelatinosa (SG) neurons of adult rat spinal cord slices. Bath-applied RTX dose-dependently increased the frequency, but not the amplitude, of spontaneous excitatory postsynaptic current (sEPSC), independent of its application time. In about a half of the neurons tested, this effect was accompanied by an inward current at -70 mV that was sensitive to glutamate-receptor antagonists. Repeated application of RTX did not affect excitatory transmission. RTX was more potent than capsaicin but showed similar efficacy. RTX activity could be blocked by capsazepine or SB-366791, a TRPV1 antagonist, but not tetrodotoxin, a Na(+)-channel blocker, and could be inhibited by pretreatment with capsaicin but not the TRPA1 agonist, allyl isothiocyanate. RTX enhances the spontaneous release of L-glutamate from nerve terminals with similar efficacy as capsaicin and produces a membrane depolarization by activating TRPV1 in the SG, with fast desensitization and slow recovery from desensitization. These results indicate a mechanism by which RTX can modulate excitatory transmission in SG neurons to regulate nociceptive transmission.
Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
C-Y
CY
Jiang
T
T
Fujita
H-Y
HY
Yue
L-H
LH
Piao
T
T
Liu
T
T
Nakatsuka
E
E
Kumamoto
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013376:Substantia Gelatinosa / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D050916:TRPV Cation Channels / Q000819:agonists* / Q000037:antagonists & inhibitors
D004224:Diterpenes; D017879:Isothiocyanates; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D018698:Glutamic Acid; C024353:resiniferatoxin; C004471:allyl isothiocyanate; D002211:Capsaicin