title: Aminoethoxydiphenyl borate and flufenamic acid inhibit Ca2+ influx through TRPM2 channels in rat dorsal root ganglion neurons activated by ADP-ribose and rotenone.
abstract: Exposure to oxidative stress causes health problems, including sensory neuron neuropathy and pain. Rotenone is a toxin used to generate intracellular oxidative stress in neurons. However, the mechanism of toxicity in dorsal root ganglion (DRG) neurons has not been characterized. Melastatin-like transient receptor potential 2 (TRPM2) channel activation and inhibition in response to oxidative stress, ADP-ribose (ADPR), flufenamic acid (FFA) and 2-aminoethoxydiphenyl borate (2-APB) in DRG neurons are also not clear. We tested the effects of FFA and 2-APB on ADPR and rotenone-induced TRPM2 cation channel activation in DRG neurons of rats. DRG neurons were freshly isolated from rats and studied with the conventional whole-cell patch-clamp technique. Rotenone, FFA and 2-APB were extracellularly added through the patch chamber, and ADPR was applied intracellularly through the patch pipette. TRPM2 cation currents were consistently induced by ADPR and rotenone. Current densities of the neurons were higher in the ADPR and rotenone groups than in control. The time courses (gating times) in the neurons were longer in the rotenone than in the ADPR group. ADPR and rotenone-induced TRPM2 currents were totally blocked by 2-APB and partially blocked by FFA. In conclusion, TRPM2 channels were constitutively activated by ADPR and rotenone, and 2-APB and FFA induced an inhibitory effect on TRPM2 cation channel currents in rat DRG neurons. Since oxidative stress is a common feature of neuropathic pain and diseases of sensory neurons, the present findings have broad application to the etiology of neuropathic pain and diseases of DRG neurons.
authors.affiliation: Department of Biophysics, Faculty of Medicine, University of Suleyman Demirel, 32260, Isparta, Turkey. mnaziroglu@med.sdu.edu.tr
authors.forename: Mustafa
authors.initials: M
authors.lastname: Nazıroğlu
authors.forename: Cemil
authors.initials: C
authors.lastname: Özgül
authors.forename: Ömer
authors.initials: Ö
authors.lastname: Çelik
authors.forename: Bilal
authors.initials: B
authors.lastname: Çiğ
authors.forename: Ercan
authors.initials: E
authors.lastname: Sözbir
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000494:pharmacology*; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D005439:Flufenamic Acid / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000494:pharmacology*; D050053:TRPM Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology*
chemical_list: D001896:Boron Compounds; D050053:TRPM Cation Channels; C557080:Trpm2 protein, rat; D014475:Uncoupling Agents; D012402:Rotenone; D000246:Adenosine Diphosphate Ribose; D005439:Flufenamic Acid; C109986:2-aminoethoxydiphenyl borate