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Aminoethoxydiphenyl borate and flufenamic acid inhibit Ca2 influx through TRPM2 channels in rat dorsal root ganglion neurons activated by ADP ribose and rotenone     
Yazarlar
Mustafa Nazıroğlu
Süleyman Demirel Üniversitesi, Türkiye
Cemil Özgül
Ömer Çelik
Süleyman Demirel Üniversitesi, Türkiye
Doç. Dr. Bilal ÇİĞ Doç. Dr. Bilal ÇİĞ
Süleyman Demirel Üniversitesi, Türkiye
Ercan Sözbir
Özet
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.
Anahtar Kelimeler
ADP-ribose | Antagonists | Dorsal root ganglion neuron | Oxidative stress | TRPM2 channel
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı JOURNAL OF MEMBRANE BIOLOGY
Dergi ISSN 0022-2631
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili İngilizce
Basım Tarihi 05-2011
Cilt No 241
Sayı 2
Sayfalar 69 / 75
Doi Numarası 10.1007/s00232-011-9363-9