title: Hydrogen sulfide increases excitability through suppression of sustained potassium channel currents of rat trigeminal ganglion neurons.
abstract: BACKGROUND
  Hydrogen sulfide (H2S), an endogenous gaseotransmitter/modulator, is becoming appreciated that it may be involved in a wide variety of processes including inflammation and nociception. However, the role and mechanism for H2S in nociceptive processing in trigeminal ganglion (TG) neuron remains unknown. The aim of this study is to investigate distribution of endogenous H2S synthesizing enzyme cystathionine-β-synthetase (CBS) expression and role of H2S on excitability and voltage-gated potassium channels of TG neurons.
  
  
  METHODS
  Immunofluorescence studies were carried out to determine whether CBS was co-expressed in Kv1.1 or Kv1.4-positive TG neurons. Whole cell patch clamp recordings were employed on acutely isolated TG neurons from adult male Sprague Dawley rats (6-8 week old). von Frey filaments were used to examine the pain behavioral responses in rats following injection of sodium hydrosulfide.
  
  
  RESULTS
  In rat TG, 77.3±6.6% neurons were immunoreactive for CBS, 85.1±3.8% for Kv1.1 and 97.8±1.1% for Kv1.4. Double staining showed that all CBS labeled cells were Kv1.1 and Kv1.4 positive, but only 92.2±6.1% of Kv1.1 and 78.2±9.9% of Kv1.4 positive cells contained CBS. Application of H2S donor NaHS (250 μM) led to a significant depolarization of resting membrane potential recorded from TG neurons. NaHS application also resulted in a dramatic reduction in rheobase, hyperpolarization of action potential threshold, and a significant increase in the number of action potentials evoked at 2X and 3X rheobase stimulation. Under voltage-clamp conditions, TG neurons exhibited transient A-type (IA) and sustained outward rectifier K+ currents (IK). Application of NaHS did suppress IK density while did not change IA density of TG neurons (n=6). Furthermore, NaHS, a donor of hydrogen sulfide, produced a significant reduction in escape threshold in a dose dependent manner.
  
  
  CONCLUSIONS
  These data suggest that endogenous H2S generating enzyme CBS was co-localized well with Kv1.1 and Kv1.4 in TG neurons and that H2S produces the mechanic pain and increases neuronal excitability, which might be largely mediated by suppressing IK density, thus identifying for the first time a specific molecular mechanism underlying pain and sensitization in TG.
authors: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Pain Research & Therapy, Soochow University, Suzhou 215123, China.
authors: Xingmei
authors: X
authors: Feng
authors: You-Lang
authors: YL
authors: Zhou
authors: Xiaowen
authors: X
authors: Meng
authors: Fei-Hu
authors: FH
authors: Qi
authors: Wei
authors: W
authors: Chen
authors: Xinghong
authors: X
authors: Jiang
authors: Guang-Yin
authors: GY
authors: Xu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects*; D051662:Kv1.1 Potassium Channel / Q000378:metabolism*; D051665:Kv1.4 Potassium Channel / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*
chemical_list: C489293:Kcna1 protein, rat; D051665:Kv1.4 Potassium Channel; D051662:Kv1.1 Potassium Channel; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide