title: TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase.
abstract: We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na(+)-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.
authors.affiliation: Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Lian-Hua
authors.initials: LH
authors.lastname: Piao
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Fujita
authors.forename: Chang-Yu
authors.initials: CY
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Hai-Yuan
authors.initials: HY
authors.lastname: Yue
authors.forename: Terumasa
authors.initials: T
authors.lastname: Nakatsuka
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kumamoto
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D017487:Ankyrins; D015220:Calcium Channels / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D008012:Lidocaine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013376:Substantia Gelatinosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels
chemical_list: D000779:Anesthetics, Local; D017487:Ankyrins; D015220:Calcium Channels; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D018698:Glutamic Acid; D011343:Procaine; D008012:Lidocaine