Hydrogen sulfide (H2S) is an important biomolecule for its role in mediating redox homeostasis and signaling biological processes. The study of biological sulfide is currently impeded by a lack of tools available that adequately address the questions currently facing the field. The most pressing of these questions are: how does H2S signal biological processes. To produce tools for studying H2S, chemiluminescent scaffolds were designed to study both H2S producing enzymes and directly measure free H2S. Additionally, small molecule organic persulfides were synthesized and characterized in order to study the properties and reactivity of H2S signaling species. By creating methods to directly measure biological H2S and creating model systems to investigate the active signaling species, the biological reactivity of H2S can be better understood. The luminescent methods for detecting H2S were developed in order to avoid photodecomposition inherent with fluorescent methods while still providing a spectroscopic readout for performing measurements in cells. D-cysteine concentrations can be measured using luciferin bioluminescence, and utilized to back out the H2S producing activity of DAO. Free H2S was measured using luminol derived chemiluminescence. The luminol scaffolds were studied in depth to determine what makes an H2S probe selective for H2S in order to inform the design of future H2S probes. Sulfide signaling processes were investigated using organic persulfide model systems. We found that under reducing conditions persulfides liberate free H2S, and that under basic conditions they decompose. The decomposition pathway is governed by substitution at the -carbon, which dictates the steric accessibility of the inner sulfur atom to act as an electrophile. Persulifdes do not react with acids, and are easily tagged by electrophiles to form disulfides. Persulfides are sufficiently reducing to generate NO from nitrite, facilitating cross-talk between multiple signaling species. This cross talk is mediated by formation of perthionitrite, which may function as an independent signaling species.

Orientador: Heloísa Helena de Araújo Ferreira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T22:34:56Z (GMT). No. of bitstreams: 1 Benetti_LeticiaRegina_M.pdf: 4223548 bytes, checksum: 318ea90daa8192a20e71e361921955fd (MD5) Previous issue date: 2012 / Resumo: Estudos têm demonstrado que o sulfeto de hidrogênio (H2S) tem um importante papel em vários aspectos da fisiologia e da patologia de diferentes doenças. Este estudo teve como objetivo investigar a ação do H2S nos marcadores de estresse oxidativo e sua interação com o oxido nítrico ('NO) na inflamação alérgica pulmonar de camundongos. Camundongos BALB/c foram sensibilizados com ovalbumina (OVA) e tratados com o doador de H2S, hidrosulfeto de sódio (NaHS), ou com o inibidor da oxido nítrico sinatase induzível (iNOS), 1400W, 30 minutos e 2h antes do desafio com OVA, respectivamente. Vinte e quatro, 48 e 96h após o desafio, os animais foram sacrificados e coletou-se o lavado broncoalveolar para contagem total e diferencial de leucócitos e dosagem dos níveis de NOx; os pulmões foram homogeneizados para análise da expressão das proteínas iNOS, MnSOD e Cu/ZnSOD por Western blotting e verificação dos níveis da 3-nitrotirosina (3-NT) por Slot blotting. A atividade da iNOS foi analisada pela conversão de L-arginina para L-citrulina. Os resultados demonstraram que o tratamento com NaHS inibiu a migração de neutrófilos para os pulmões de camundongos sensibilizados em 24h e 48h e de eosinófilos em 48h após o desafio alergênico, quando comparados com os camundongos controles (não tratados). De maneira semelhante, o tratamento com 1400W inibiu o influxo de eosinófilos para o pulmão dos camundongos alérgicos em 48h. O controles em 48h que foi inibida tanto pelo tratamento com NaHS como pelo 1400W. Neste período,desafio com OVA provocou aumento da expressão da iNOS nos pulmões dos animais observou-se aumento da atividade da NOS Ca -independente nos pulmões dos camundongos controles. O tratamento com 1400W, mas não com NaHS, provocou redução desta atividade. Quando comparados com os animais não desafiados, os níveis de NOx nos controles estavam aumentados em todos períodos estudados. Os tratamentos com 1400W e NaHS reduziram seus níveis em 48h e 96h, respectivamente. A expressão da 3-NT foi reduzida pelo 1400W em 48h, mas nenhum efeito foi observado com o NaHS. O desafio com OVA nos animais controles não alterou a expressão de MnSOD, mas provocou aumento da expressão da Cu/ZnSOD em 48h após o desafio com OVA. Neste período, o NaHS reduziu a expressão da MnSOD e o 1400W a expressão da Cu/ZnSOD. Estes resultados demonstram que o efeito anti-inflamatório do H2S na asma ao inibir a migração de eosinófilos e neutrófilos para os pulmões não é decorrente de mecanismos relacionados à via do 'NO. Se a redução da expressão da MnSOD verificada nos animais tratados com NaHS está relacionada à apoptose de eosinófilos e/ou neutrófilos e, consequentemente, à diminuição do conteúdo destas células no LBA precisa ser verificado / Abstract: Studies have shown that hydrogen sulfide (H2S) has an important role in various physiological and pathological aspects of different diseases. In this study, we verified the influence of H2S on oxidative stress and its interaction the nitric oxide ('NO) pathway in the allergic lung inflammation of mice. BALB/c mice were sensitized with ovalbumin (OVA) and treated the H2S donor, sodium hydrosulfide (NaHS), or with the inducible nitric oxide synthase (iNOS) inhibitor, 1400W, 30 minutes and 2h before OVA-challenge, respectively. Twenty-four, 48 and 96h after challenge, mice were sacrificed and the bronchoalveolar lavage (BAL) was collected to investigate the total and differential leukocyte counts and the NOx leveis. The lungs were homogenized to analyze the iNOS, MnSOD and Cu/ZnSOD protein expressions by Western blotting and the 3-nitrotyrosine (3-NT) leveis by Slot blotting. The iNOS activity was determined by conversion of L-arginine to L-citrulline. Results showed that NaHS-treatment of sensitized mice inhibited neutrophil migration at 24h and 48h, as well as the eosinophil influx to the lungs at 48h after allergen challenge when compared with control mice (untreated). Similarly, 1400W-treatment reduced the content of eosinophils in the BAL of allergic mice at 48 hours. OVA-challenge caused an increase in iNOS expression in the lungs of control mice at 48 hours, which was inhibited by NaHS or 1400W treatments. At this time, an increase in Ca+-independent NOS activity was observed in the lungs of control mice. The 1400W-treatment, but not NaHS-treatment, caused a reduction in this activity. When compared with non-challenged mice, NOx leveis were increased in coritrols at ali times studied. Treatment with 1400W or NaHS reduced their leveis at 48h and 96h, respectively. The 3-NT expression was reduced by 1400W at 48 hours, but no effect was observed with the NaHS-treatment. The OVA-challenge of control mice did not modify the MnSOD expression, but caused increased of Cu/ZnSOD expression at 48 hours. However, the NAHS reduced the MnSOD expression and 1400W inhibited the Cu/ZnSOD expression at this time. These results demonstrated that the anti-inflammatory effect of H2S in asthma by inhibiting eosinophils and neutrophil migration to the lungs is not due to mechanisms associated with 'NO pathway. If the reduced MnSOD expression observed in NaHS-treated mice is related with the eosinophil apoptosis and, consequently, decrease of inflammatory cells content in the BAL needs to be studied / Mestrado / Farmacologia / Mestre em Farmacologia

Orientador: Heloísa Helena de Araújo Ferreira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T01:09:24Z (GMT). No. of bitstreams: 1 Campos_Daiana_M.pdf: 5833117 bytes, checksum: 9ef22e0c9d416945c3eddacc3a3bb437 (MD5) Previous issue date: 2012 / Resumo: Diversos estudos mostram que o sulfeto de hidrogênio (H2S) exerce importante papel em diferentes aspectos da fisiologia e da patologia pulmonar. O objetivo deste trabalho foi investigar o efeito do tratamento com um doador de H2S no estresse oxidativo produzido pela inflamação alérgica pulmonar. Camundongos BALB/c foram sensibilizados com ovalbumina (OVA) e tratados com NaHS 30 minutos antes de cada desafio com OVA. Os animais sofreram eutanásia em 24h- 144h após o desafio com OVA, quando foi coletado o lavado bronchoalveolar, para contagem total e diferencial de eosinófilos, e retirados os pulmões. Os pulmões foram homogeneizados para análise da atividade das enzimas aconitase (que possui relação inversa com a produção de O2o- intracelular), fumarase, superóxido dismutase (SOD), catalase, glutationa peroxidase (GPx), glutationa redutase (GR) e para a verificação do conteúdo de substâncias reativas ao ácido tiobarbitúrico (TBARS) por método colorimétrico. Os níveis de glutationa reduzida (GSH) e glutationa oxidada (GSSG) foram determinados por cromatografia. Os resultados dos camundongos não tratados (controle) mostraram que o aumento do conteúdo de eosinófilos para os pulmões ocorreu como uma resposta bifásica entre 48h/96h e 144h após o desafio com OVA. Nestes horários, observamos no grupo controle redução na atividade da aconitase, que foi acompanhada do aumento da peroxidação lipídica (TBARS). A atividade da enzima SOO estava aumentada nestes animais a partir de 24h, seguida de uma redução em 144h, enquanto que as atividades das enzimas catalase e GR estavam aumentadas somente em 48h. Não foram observadas modificações na atividade da GPx, assim como nos níveis de GSH e GSSG, em nenhum dos períodos estudados. O tratamento dos camundongos alérgicos com NaHS reduziu o infiltrado de eosinófilos em 48h e 144h após o desafio antigênico, recuperou a atividade da aconitase e reduziu a peroxidação lipídica, quando comparado aos controles. Nestes horários, o tratamento com o NaHS também aumentou as atividades das enzimas SOD, GPx e GR e os níveis de GSH. Diferente destes resultados verificou-se uma redução da atividade da catalase em 48h, quando comparado ao grupo controle. Em conclusão, nossos resultados sugerem que o H2S exerce efeito benéfico na inflamação alérgica pulmonar ao inibir o recrutamento de eosinófilos para os pulmões. Do mesmo modo, produz um importante efeito no estresse oxidativo ao reduzir a peroxidação lipídica e a produção de O2o- intracelular (determinado pela atividade da aconitase) e ao aumentar a atividade da SOD. As atividades das enzimas GPx e GR também estavam aumentadas contribuindo para o aumento de GSH. Deste modo, o NaHS (e provavelmente outros doadores de H2S) podem apresentar potencialmente importante uso terapêutico para o tratamento de doenças pulmonares caracterizadas pela presença de células inflamatórias e desbalanceamento do equilíbrio oxidante/antioxidante / Abstract: Several studies show that the hydrogen sulfide (H2S) plays an important role in different aspects of lung physiology and pathology. The aim of this study was to investigate a H2S-donor treatment on the oxidative stress produced by pulmonary allergic inflammation. BALB/c mice were sensitized with ovalbumin (OVA) and treated with NaHS, 30 minutes before each OVA-challenge. The animals were sacrificed at 24h-144h after challenge, when bronchoalveolar lavage was collected for total and differential eosinophils counts and the lungs were collected. The lungs were homogenized for aconitase (that has inverse correlation with intracelular O2o- production), fumarase, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR) enzymes analysis and thiobarbituric acid reactive substances (TBARS) measurement by colorimetric methods. The determination of reduced glutathione (GSH) and glutathione disulfide (GSSG) levels were done by chromatography. The results from untreated (control) mice showed that an increase of eosinophil influx to the lungs happened as a biphasic response between 48h/96h and at 144h after OVA-challenge. At the same hours we observed in this group a reduction in aconitase levels that were accompanied by lipid peroxidation (TBARS) increase. The SOD activity was increased in control animals at 24h followed by reduction at 144h, whereas catalase and GR activities were increased only at 48h. There were no changes in GPx activity, neither in GSH nor in GSSG levels at any time- studied. NaHS-treatment reduced eosinophils infiltration at 48h and 144h after antigen challenge when it was observed a recovery in the aconitase activity and a decrease in TBARS lung contents as compared to control mice. It was also observed in these times after antigen challenge increases in SOD, GPx as well as GR activities and in GSH levels. Differing from these results, NaHS-treatment reduced catalase activity at 48h, as compared to control group. In conclusion, our results suggest that NaHS exerts beneficial effect on allergic pulmonary inflammation by inhibiting the eosinophils recruitment to the lungs of mice after OVA-challenge. It also produces a significant effect on oxidative stress by reducing lipid peroxidation and intracelular O2o- production (measured by aconitase activities) as well as by increasing SOD activity. The GPx and GR activities were also improved, and that could account for GSH increase. Therefore, NaHS (and probably others H2S donors) may emerge as potentially useful therapeutic tools for treatment of lung diseases characterized by the presence of inflammatory cells and oxidant/antioxidant imbalance / Mestrado / Farmacologia / Mestra em Farmacologia

In recent years, the association between inflammatory bowel diseases (IBDs) and gut microbiota has been extensively studied in adults using post-treatment cohorts of patients. However, microbial composition and functional interplay between host genetics and microorganisms in newly diagnosed early IBD onset remain poorly defined. Using colonoscopic mucosal washes to collect mucosal-luminal microbiota from different intestinal locations, we studied the gut microbiome in a large number of children with either Crohn’s disease (CD) or ulcerative colitis (UC). Although no significant difference in the diversity was evident between the gut microbiota of IBD-affected and control children, the microbiome of IBD subjects is characterized by an increased abundance of potent hydrogen sulfide (H2S) producers and decreased abundance of beneficial butyrate producers. Microbiota and proteomic profiling revealed that the abundance of Atopobium parvulum, a potent H2S producer, was associated with increased CD severity and a concurrent reduction in the expression of the host H2S detoxification pathway. Gnotobiotic and conventionalized colitis-susceptible interleukin-10-deficient (Il-10-/-) mice showed that A. parvulum induces severe colitis, a phenotype requiring the presence of the gut microbiota. In addition, administration of bismuth, an H2S scavenger, prevented A. parvulum-induced colitis in Il-10-/- mice. Our findings have identified A. parvulum as a major mediator of inflammation severity. We also reveal an imbalance between the H2S production and detoxification in the gastrointestinal tract of pediatric IBD patients. Altogether, our findings provide new avenues for diagnostics as well as therapies to treat IBD.

Toxic exposure to hydrogen sulfide (H2S) is a well-recognized hazard in agriculture, particularly in livestock operations that manage large amounts of manure. Numerous fatalities have been observed, often multiple fatalities in a single incident, due to toxic exposure to H2S from manure pits at concentrations higher than 500 ppm. Direct-reading instruments that alarm workers in the areas when H2S concentrations are high may prevent these fatalities. However, monitors that are commonly found in industries with robust safety programs are impractical for agricultural use as they are often prohibitively expensive and require regular maintenance and calibration that may be above the expertise level of agricultural workers. In more recent years, manufacturers marketed simpler models of direct-reading H2S monitors as “low-maintenance” or “maintenance-free” at a much lower cost than traditional monitors, which may cost $500 for basic models or more than $1000 for more complex models. The objective of this study was to test several models of low-cost, low-maintenance monitors in order to examine the features of each for comparison, as well as to test the performance of these monitors with no maintenance over time while under constant exposure to low levels of H2S. Two types of monitors were examined: qualitative monitors that were lowest-cost (around $100) and provided only alarm settings with no concentration displayed (Honeywell BW Clip and MSA Altair), and quantitative monitors that cost slightly more (around $200) but displayed concentration readings (Dräger Pac 3500 and Industrial Scientific T40 Rattler). All models were exposed to H2S for a test period of 4 months, at concentrations slightly higher than typical background concentrations to simulate expected monitor exposure for a year in a barn. The performance of qualitative (‘alarm-only’) monitors declined faster than over the course of the simulated barn year than the quantitative monitors, with both models of qualitative meters failing to alarm at the high setting before the test period was complete. The quantitative (‘concentration-display’) models showed fewer effects from long-term exposure over the duration of testing, but both models exhibited inaccuracies in the concentration readings when compared to calibration gas concentrations. The T40 Rattler provided consistently higher readings (+2.3 ppm) than the calibration gas concentration, while the Pac 3500 showed consistently lower readings (-3.4 ppm) than the calibration gas concentration. Serious acute health effects for H2S are not typically observed until exposure to concentrations above 500 ppm, so inaccuracies of this small magnitude are relatively insignificant. Though each of the test monitors is advertised to be maintenance-free for two years, this study found that failures occurred within one simulated year in a barn. Bump checks should be performed regularly to ensure the monitor reacts to the presence of H2S appropriately, even when the manufacturer’s literature may say otherwise. Most importantly, agricultural workers should always inspect and bump check these monitors prior to any potentially high-risk activity such as manure agitation or pumping to ensure that the monitor is still providing the protection needed from a potentially toxic release of H2S. This study tested each of these models within a clean chamber at room temperature to isolate the effects of long-term exposure to H2S. In an actual barn, these monitors may be exposed to variations in temperature and humidity, as well as other barn contaminants such as ammonia, dust, and chemicals. Each of these other exposures could also affect the performance of these monitors over time, and should be considered when storing and using these monitors. Furthermore, the potential interactions from other exposures is an opportunity for future study to better understand how these interactions may affect sensor performance in an agricultural environment.

The aim of this diploma thesis is to research the possibilities of an odor regulation in a sewerage system. The first part of the thesis is devoted to legislation in sewege odor problematics. The second part includes description of the cause of the odor and methodology related to a hydrogen sulfide elimination either from sewerage atmosphere or straight from waste water. The next part examines the results of a survey, which was given to operators of the sewerage system. The survey examined the cause of an odor, its control and possible solutions of an odor in a sewerage system. Practical part is devoted to a given geographical area, where these problems have occurred the past. In this area the measuring of hydrogen sulfide presence took place by adding chemicals into waste water. From the collected data an evaluation was made. This can serve as a possible recommendation to sewege operators.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a widely used class of drugs, due in part to the effective anti-inflammatory and analgesic properties they exhibit. Unfortunately, NSAIDs also exhibit substantial gastrointestinal (GI) toxicity. The mechanisms underlying the ability of NSAIDs to cause ulceration in the stomach and proximal duodenum are well understood, and this injury can largely be prevented through the suppression of gastric acid secretion by proton pump inhibitors (PPIs) or histamine H2 receptor antagonists (H2RAs). In contrast, the pathogenesis of small intestinal injury induced by NSAIDs (i.e., NSAID-enteropathy) is poorly understood, and there are no proven-effective therapies. This is a major clinical concern as NSAID-induced enteropathy and bleeding occur more frequently than NSAID-induced gastropathy, and is associated with significantly higher rates of morbidity and mortality. There is clear evidence that indicates important contributions to NSAID-enteropathy by bile, enteric bacteria, and the enterohepatic circulation of NSAIDs. However, it is not clear which of these mechanisms is/are the primary driver(s) of intestinal damage and injury. There is also evidence that hydrogen sulfide (H2S) can protect the GI mucosa from ulceration and reduce the severity of NSAID-induced GI damage, although the mechanisms of H2S-induced intestinal protection remain to be determined. Therefore, the central aim of this thesis was to evaluate the roles of bile, enteric bacteria, and the enterohepatic circulation of NSAIDs in the pathogenesis of NSAID-enteropathy, and to investigate the ability of H2S to protect the small intestine from NSAID-induced damage. Chapter 1 is an introduction to the relevant literature and Chapter 2 is an outline of the thesis scope and objectives. In Chapter 3, I demonstrated that the co-administration of an H2S-releasing agent protected rats from NSAID-induced enteropathy, in part by preventing NSAID-induced dysbiosis and bile cytotoxicity. In Chapter 4 and 5, I established that the co-administration of PPIs and H2RAs exacerbated NSAID-enteropathy in part by causing intestinal dysbiosis and enhanced bile cytotoxicity. Lastly, I demonstrated that the small intestine-sparing effects of an H2S-releasing NSAID, ATB-346, are partly attributable to the reduced enterohepatic circulation of ATB-346 or the naproxen liberated from this drug (Chapter 5). In summary, the work presented in this thesis provided novel understanding of the complicated pathogenesis of NSAID-enteropathy by confirming that the nature of the bile, the enterohepatic circulation of NSAIDs, and the nature of the intestinal microbiota are of paramount importance. In addition, the results also demonstrated that hydrogen sulfide represents an effective preventative therapy for NSAID-enteropathy and that H2S-releasing NSAIDs, such as ATB-346, have remarkable preclinical safety. / Thesis / Doctor of Philosophy (PhD)

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 1980 / Vita. / Bibliography: leaves 269-273. / by Selahattin Gültekin. / Ph. D. / Ph. D. Massachusetts Institute of Technology, Department of Chemical Engineering

Hydrogen sulfide (H2S), a major odorous component emitted from construction and demolition debris landfills, has received increasing attention. Besides its unpleasant odor, long-term exposure to a very low concentration of H2S can cause a public health issue. Although cover materials such as soil and compost are recommended to be used routinely to control an odor problem from the landfills, the problem still remains. Autotrophic denitrification may have environmental applications including treatment of water, groundwater, wastewater or gaseous streams contaminated with sulfur and/or nitrogen compounds. However, there have been no studies reported in the literature on H2S removal using autotrophic denitrification from landfills. This study, therefore, investigated the application of autotrophic denitrification incorporated into landfill covers in order to evaluate the feasibility of controlling H2S emissions generated from landfills. Research was investigated by two techniques, microcosm and laboratory-scale column studies. The microcosm experiments were conducted to evaluate the kinetics of autotrophic denitrification in various cover materials with H2S-nitrate as electron donor-acceptor couple. Cover materials including soil, compost and sand were tested and nitrate was added. Based on the microcosm study results, the addition of nitrate into soil and compost can stimulate indigenous autotrophic denitrifying bacteria which are capable of H2S oxidation biologically under anoxic conditions. Results also demonstrated that some amount of H2S can be removed physically and chemically by soil or compost. There was no H2S removal observed in sand microcosms. Rapid H2S oxidation to sulfate was achieved, especially in soil. Zero-order kinetics described the H2S oxidation rate in soil and compost microcosms. The rates of sulfide oxidation under autotrophic denitrification in soil and compost were 2.57 mg H2S/d-g dry soil and 0.17 mg H2S/d-g dry compost, respectively. To further explore H2S removal in a landfill biocover, two sets of column experiments were run. The first set of columns contained seven cm of soil. The autotrophic column was prepared with 1.94 mg KNO3/g dry soil; an identical control column was prepared without nitrate. A gas stream was introduced to the columns with a H2S concentration of 930 ppm. The second set contained seven cm of soil, with both an autotrophic (0.499 mg KNO3/g dry soil) and a control column. Influent H2S concentration was 140 ppm for the second set. Column studies supported the results of microcosm studies; removal of H2S was observed in all columns due to the capacity for soil to absorb H2S, however autotrophic columns removed significantly more. The higher concentration of H2S resulted in partial oxidation to elemental sulfur, while sulfate was found at levels predicted by stoichiometric relationships at the lower concentration. H2S oxidation in the column with higher loading was found to follow zero-order kinetics. The rate of H2S oxidation was 0.46 mg H2S removed/d-g dry soil. Economic comparison of cover systems including autotrophic denitrification, soil amended with lime, fine concrete, and compost covers were analyzed. Based on a case-study landfill area of 0.04 km2, the estimated H2S emissions of 80,900 kg over the 15-year period and costs of active cover system components (ammonium nitrate fertilizer, lime, concrete and compost), autotrophic denitrification cover was determined to be the most cost-effective method for controlling H2S emissions from landfills.

No / The importance of H2S as a physiological signaling molecule continues to develop, and ion channels are emerging as a major family of target proteins through which H2S exerts many actions. The purpose of the present study was to investigate its effects on T-type Ca2+ channels. Using patch-clamp electrophysiology, we demonstrate that the H2S donor, NaHS (10 μM−1 mM) selectively inhibits Cav3.2 T-type channels heterologously expressed in HEK293 cells, whereas Cav3.1 and Cav3.3 channels were unaffected. The sensitivity of Cav3.2 channels to H2S required the presence of the redox-sensitive extracellular residue H191, which is also required for tonic binding of Zn2+ to this channel. Chelation of Zn2+ with N,N,N′,N′-tetra-2-picolylethylenediamine prevented channel inhibition by H2S and also reversed H2S inhibition when applied after H2S exposure, suggesting that H2S may act via increasing the affinity of the channel for extracellular Zn2+ binding. Inhibition of native T-type channels in 3 cell lines correlated with expression of Cav3.2 and not Cav3.1 channels. Notably, H2S also inhibited native T-type (primarily Cav3.2) channels in sensory dorsal root ganglion neurons. Our data demonstrate a novel target for H2S regulation, the T-type Ca2+ channel Cav3.2, and suggest that such modulation cannot account for the pronociceptive effects of this gasotransmitter. / This work was supported by the British Heart Foundation, the Medical Research Council, and the Hebei Medical University