Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2015; 21(16): 4840-4851
Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.4840
Hydrogen sulfide-induced enhancement of gastric fundus smooth muscle tone is mediated by voltage-dependent potassium and calcium channels in mice
Xiang-Min Meng, Xu Huang, Chun-Mei Zhang, Dong-Hai Liu, Hong-Li Lu, Young-chul Kim, Wen-Xie Xu
Xiang-Min Meng, Xu Huang, Chun-Mei Zhang, Dong-Hai Liu, Hong-Li Lu, Wen-Xie Xu, Department of Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China
Young-chul Kim, Department of Physiology, Chungbuk National University College of Medicine, Chungbuk 361-763, South Korea
Author contributions: Meng XM, Huang X and Zhang CM performed the majority of experiments; Liu DH and Lu HL performed the immunohistochemistry; Kim Y was involved in editing the manuscript; and Xu WX designed the study and wrote the manuscript.
Supported by National Natural Science Foundation of China, No. 31171107, No. 31071011 and No. 31271236.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Wen-Xie Xu, Professor, Department of Physiology, Shanghai Jiaotong University School of Medicine, 800 Dongchuan Road, 328 Wenxuan Medical Building, Shanghai 200240, China.
Telephone: +86-21-34205639
Received: August 4, 2014
Peer-review started: August 5, 2014
First decision: September 15, 2014
Revised: October 17, 2014
Accepted: December 19, 2014
Article in press: December 22, 2014
Published online: April 28, 2015

AIM: To investigate the effect of hydrogen sulfide (H2S) on smooth muscle motility in the gastric fundus.

METHODS: The expression of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in cultured smooth muscle cells from the gastric fundus was examined by the immunocytochemistry technique. The tension of the gastric fundus smooth muscle was recorded by an isometric force transducer under the condition of isometric contraction with each end of the smooth muscle strip tied with a silk thread. Intracellular recording was used to identify whether hydrogen sulfide affects the resting membrane potential of the gastric fundus in vitro. Cells were freshly separated from the gastric fundus of mice using a variety of enzyme digestion methods and whole-cell patch-clamp technique was used to find the effects of hydrogen sulfide on voltage-dependent potassium channel and calcium channel. Calcium imaging with fura-3AM loading was used to investigate the mechanism by which hydrogen sulfide regulates gastric fundus motility in cultured smooth muscle cells.

RESULTS: We found that both CBS and CSE were expressed in the cultured smooth muscle cells from the gastric fundus and that H2S increased the smooth muscle tension of the gastric fundus in mice at low concentrations. In addition, nicardipine and aminooxyacetic acid (AOAA), a CBS inhibitor, reduced the tension, whereas Nω-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase, increased the tension. The AOAA-induced relaxation was significantly recovered by H2S, and the NaHS-induced increase in tonic contraction was blocked by 5 mmol/L 4-aminopyridine and 1 μmol/L nicardipine. NaHS significantly depolarized the membrane potential and inhibited the voltage-dependent potassium currents. Moreover, NaHS increased L-type Ca2+ currents and caused an elevation in intracellular calcium ([Ca2+]i).

CONCLUSION: These findings suggest that H2S may be an excitatory modulator in the gastric fundus in mice. The excitatory effect is mediated by voltage-dependent potassium and L-type calcium channels.

Keywords: Gastric fundus smooth muscle, Hydrogen sulfide, Tension, Voltage-dependent potassium channel, L-type calcium channel

Core tip: The results demonstrated that the cystathionine β-synthase and cystathionine γ-lyase were both expressed in cultured smooth muscle of the gastric fundus. Hydrogen sulfide (H2S) increased the tension of the gastric fundus and depolarized the resting membrane potential. H2S decreased the current of voltage dependent potassium channel and calcium channel and then increased the intracellular calcium.