title: Α-Dendrotoxin-sensitive Kv1 channels contribute to conduction failure of polymodal nociceptive C-fibers from rat coccygeal nerve.
abstract: It is known that some patients with diabetic neuropathy are usually accompanied by abnormal painful sensations. Evidence has accumulated that diabetic neuropathic pain is associated with the hyperexcitability of peripheral nociceptors. Previously, we demonstrated that reduced conduction failure of polymodal nociceptive C-fibers and enhanced voltage-dependent sodium currents of small dorsal root ganglion (DRG) neurons contribute to diabetic hyperalgesia. To further investigate whether and how potassium channels are involved in the conduction failure, α-dendrotoxin (α-DTX), a selective blocker of the low-threshold sustained Kv1 channel, was chosen to examine its functional capability in modulating the conduction properties of polymodal nociceptive C-fibers and the excitability of sensory neurons. We found that α-DTX reduced the conduction failure of C-fibers from coccygeal nerve in vivo accompanied by an increased initial conduction velocity but a decreased activity-dependent slowing of conduction velocity. In addition, the number of APs evoked by step currents was significantly enhanced after the treatment with α-DTX in small-diameter sensory neurons. Further study of the mechanism indicates α-DTX-sensitive K(+) current significantly reduced and the activation of this current in peak and steady state shifted to depolarization for diabetic neurons. Expression of Kv channel subunits Kv1.2 and Kv1.6 was downregulated in both small dorsal root ganglion neurons and peripheral C-fibers. Taken together, these results suggest that α-DTX-sensitive Kv1 channels might play an important role in regulating the conduction properties of polymodal nociceptive C-fibers and firing properties of sensory neurons.
authors.affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an, People's Republic of China; Department of Psychology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Xiu-Chao
authors.initials: XC
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.affiliation: Team Nine, Brigade of Cadets, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Chun
authors.initials: C
authors.lastname: Yin
authors.affiliation: Team Nine, Brigade of Cadets, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Xi'an, People's Republic of China; and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: San-Jue
authors.initials: SJ
authors.lastname: Hu
authors.affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an, People's Republic of China; State Key Laboratory of Military Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China jhduan@fmmu.edu.cn.
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Duan
mesh_terms: D000200:Action Potentials; D000818:Animals; D002478:Cells, Cultured; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation; D004546:Elapid Venoms / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D059225:Nociception; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051637:Shaker Superfamily of Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004546:Elapid Venoms; D026902:Potassium Channel Blockers; D051637:Shaker Superfamily of Potassium Channels; C020273:dendrotoxin
keywords: C-fiber; conduction failure; diabetic; dorsal root ganglion; α-dendrotoxin sensitive K+ current