Hydrogen sulfide increases excitability through suppression of sustained potassium channel currents of rat trigeminal ganglion neurons

Molecular Pain

Guang-Yin Xu³  Xinghong Jiang³  Wei Chen²  Fei-Hu Qi²  Xiaowen Meng³  You-Lang Zhou³  Xingmei Feng¹ 

[1] Department of Stomatology, Affiliated Hospital of Nantong University, Nantong 226001, China;Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China;Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Pain Research & Therapy, Soochow University, Suzhou 215123, China

关键词: Voltage-gated potassium channels;    Excitability;    Trigeminal ganglion;    Cystathionine-β-synthase;    Hydrogen sulfide;   

Others  :  862630
DOI  :  10.1186/1744-8069-9-4

 received in 2012-07-28, accepted in 2013-02-14,  发布年份 2013

【 摘 要 】

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 (I_A) and sustained outward rectifier K⁺ currents (I_K). Application of NaHS did suppress I_K density while did not change I_A 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.

Conclusion

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 I_K density, thus identifying for the first time a specific molecular mechanism underlying pain and sensitization in TG.

【 授权许可】

   
2013 Feng et al; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Fiorucci S, Distrutti E, Cirino G, Wallace JL: The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver. Gastroenterology 2006, 131:259-271.
• [2]Kawabata A, Ishiki T, Nagasawa K, Yoshida S, Maeda Y, Takahashi T, Sekiguchi F, Wada T, Ichida S, Nishikawa H: Hydrogen sulfide as a novel nociceptive messenger. Pain 2007, 132:74-81.
• [3]Matsunami M, Tarui T, Mitani K, Nagasawa K, Fukushima O, Okubo K, Yoshida S, Takemura M, Kawabata A: Luminal hydrogen sulfide plays a pronociceptive role in mouse colon. Gut 2009, 58:751-761.
• [4]Nishimura S, Fukushima O, Ishikura H, Takahashi T, Matsunami M, Tsujiuchi T, Sekiguchi F, Naruse M, Kamanaka Y, Kawabata A: Hydrogen sulfide as a novel mediator for pancreatic pain in rodents. Gut 2009, 58:762-770.
• [5]Schemann M, Grundy D: Role of hydrogen sulfide in visceral nociception. Gut 2009, 58:744-747.
• [6]Smith DR, Dilorenzo N, Leibovich J, May ML, Quinn MJ, Homm JW, Galyean ML: Effects of sulfur and monensin concentrations on in vitro dry matter disappearance, hydrogen sulfide production, and volatile fatty acid concentrations in batch culture ruminal fermentations. J Anim Sci 2010, 88:1503-1512.
• [7]Tang G, Wu L, Wang R: Interaction of hydrogen sulfide with ion channels. Clin Exp Pharmacol Physiol 2010, 37:753-763.
• [8]Maeda Y, Aoki Y, Sekiguchi F, Matsunami M, Takahashi T, Nishikawa H, Kawabata A: Hyperalgesia induced by spinal and peripheral hydrogen sulfide: evidence for involvement of Cav3.2 T-type calcium channels. Pain 2009, 142:127-132.
• [9]Lee AT, Shah JJ, Li L, Cheng Y, Moore PK, Khanna S: A nociceptive-intensity-dependent role for hydrogen sulphide in the formalin model of persistent inflammatory pain. Neuroscience 2008, 152:89-96.
• [10]Bhatia M, Wong FL, Fu D, Lau HY, Moochhala SM, Moore PK: Role of hydrogen sulfide in acute pancreatitis and associated lung injury. FASEB J 2005, 19:623-625.
• [11]Xu GY, Winston JH, Shenoy M, Zhou S, Chen JD, Pasricha PJ: The endogenous hydrogen sulfide producing enzyme cystathionine-beta synthase contributes to visceral hypersensitivity in a rat model of irritable bowel syndrome. Mol Pain 2009, 5:44. BioMed Central Full Text
• [12]Distrutti E, Sediari L, Mencarelli A, Renga B, Orlandi S, Antonelli E, Roviezzo F, Morelli A, Cirino G, Wallace JL, Fiorucci S: Evidence that hydrogen sulfide exerts antinociceptive effects in the gastrointestinal tract by activating KATP channels. J Pharmacol Exp Ther 2006, 316:325-335.
• [13]Gold MS, Shuster MJ, Levine JD: Role of a Ca(2+)-dependent slow afterhyperpolarization in prostaglandin E2-induced sensitization of cultured rat sensory neurons. Neurosci Lett 1996, 205:161-164.
• [14]Zhu Y, Mehta K, Li C, Xu GY, Liu L, Colak T, Shenoy M, Pasricha PJ: Systemic administration of anti-NGF increases A-type potassium currents and decreases pancreatic nociceptor excitability in a rat model of chronic pancreatitis. Am J Physiol Gastrointest Liver Physiol 2012, 302:G176-G181.
• [15]Liu Y, Savtchouk I, Acharjee S, Liu SJ: Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells. J Neurophysiol 2011, 106:144-152.
• [16]Flake NM, Bonebreak DB, Gold MS: Estrogen and inflammation increase the excitability of rat temporomandibular joint afferent neurons. J Neurophysiol 2005, 93:1585-1597.
• [17]Wang H, Wei F, Dubner R, Ren K: Selective distribution and function of primary afferent nociceptive inputs from deep muscle tissue to the brainstem trigeminal transition zone. J Comp Neurol 2006, 498:390-402.
• [18]Lagares A, Li HY, Zhou XF, Avendano C: Primary sensory neuron addition in the adult rat trigeminal ganglion: evidence for neural crest glio-neuronal precursor maturation. J Neurosci 2007, 27:7939-7953.
• [19]Martenson ME, Arguelles JH, Baumann TK: Enhancement of rat trigeminal ganglion neuron responses to piperine in a low-pH environment and block by capsazepine. Brain Res 1997, 761:71-76.
• [20]Walsh KB, Zhang J: Neonatal rat cardiac fibroblasts express three types of voltage-gated K+ channels: regulation of a transient outward current by protein kinase C. Am J Physiol Heart Circ Physiol 2008, 294:H1010-H1017.
• [21]Guo W, Xu H, London B, Nerbonne JM: Molecular basis of transient outward K+ current diversity in mouse ventricular myocytes. J Physiol 1999, 521(Pt 3):587-599.
• [22]Ren K: An improved method for assessing mechanical allodynia in the rat. Physiol Behav 1999, 67:711-716.
• [23]Lee S, Zhang J: Heterogeneity of macrophages in injured trigeminal nerves: cytokine/chemokine expressing vs. phagocytic macrophages. Brain Behav Immun 2012, 26:891-903.
• [24]Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL: Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994, 53:55-63.
• [25]Wood CM, Bergman HL, Bianchini A, Laurent P, Maina J, Johannsson OE, Bianchini LF, Chevalier C, Kavembe GD, Papah MB, Ojoo RO: Transepithelial potential in the Magadi tilapia, a fish living in extreme alkalinity. J Comp Physiol B 2012, 182:247-258.
• [26]Kawasaki H, Palmieri C, Avoli M: Muscarinic receptor activation induces depolarizing plateau potentials in bursting neurons of the rat subiculum. J Neurophysiol 1999, 82:2590-2601.
• [27]Glinn M, Ni B, Paul SM: Characterization of Na(+)-dependent phosphate uptake in cultured fetal rat cortical neurons. J Neurochem 1995, 65:2358-2365.
• [28]Guo Q, Jin S, Wang XL, Wang R, Xiao L, He RR, Wu YM: Hydrogen sulfide in the rostral ventrolateral medulla inhibits sympathetic vasomotor tone through ATP-sensitive K+ channels. J Pharmacol Exp Ther 2011, 338:458-465.
• [29]Mikami Y, Shibuya N, Kimura Y, Nagahara N, Yamada M, Kimura H: Hydrogen sulfide protects the retina from light-induced degeneration by the modulation of Ca2+ influx. J Biol Chem 2011, 286:39379-39386.
• [30]Kabil H, Kabil O, Banerjee R, Harshman LG, Pletcher SD: Increased transsulfuration mediates longevity and dietary restriction in Drosophila. Proc Natl Acad Sci U S A 2011, 108:16831-16836.
• [31]Kimura H: Hydrogen sulfide induces cyclic AMP and modulates the NMDA receptor. Biochem Biophys Res Commun 2000, 267:129-133.
• [32]Xu GY, Winston JH, Chen JD: Electroacupuncture attenuates visceral hyperalgesia and inhibits the enhanced excitability of colon specific sensory neurons in a rat model of irritable bowel syndrome. Neurogastroenterol Motil 2009, 21:1302-e1125.
• [33]Le Franc Y, Le Masson G: Multiple firing patterns in deep dorsal horn neurons of the spinal cord: computational analysis of mechanisms and functional implications. J Neurophysiol 2010, 104:1978-1996.
• [34]Vydyanathan A, Wu ZZ, Chen SR, Pan HL: A-type voltage-gated K+ currents influence firing properties of isolectin B4-positive but not isolectin B4-negative primary sensory neurons. J Neurophysiol 2005, 93:3401-3409.
• [35]Takeda M, Tsuboi Y, Kitagawa J, Nakagawa K, Iwata K, Matsumoto S: Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain. Mol Pain 2011, 7:5. BioMed Central Full Text
• [36]Patacchini R, Santicioli P, Giuliani S, Maggi CA: Hydrogen sulfide (H2S) stimulates capsaicin-sensitive primary afferent neurons in the rat urinary bladder. Br J Pharmacol 2004, 142:31-34.
• [37]Sonner PM, Lee S, Ryu PD, Lee SY, Stern JE: Imbalanced K+ and Ca2+ subthreshold interactions contribute to increased hypothalamic presympathetic neuronal excitability in hypertensive rats. J Physiol 2011, 589:667-683.
• [38]Surges R, Freiman TM, Feuerstein TJ: Input resistance is voltage dependent due to activation of Ih channels in rat CA1 pyramidal cells. J Neurosci Res 2004, 76:475-480.
• [39]Meier S, Tavraz NN, Durr KL, Friedrich T: Hyperpolarization-activated inward leakage currents caused by deletion or mutation of carboxy-terminal tyrosines of the Na+/K+-ATPase alpha subunit. J Gen Physiol 2010, 135:115-134.