H2S relaxes isolated human airway smooth muscle cells via the sarcolemmal KATP channel

作者: Breann DeSantiago , Danielle Y. Lee , Guangdong Yang , Jae Yeon Kim , D. Brian Foster

DOI: 10.1016/J.BBRC.2014.02.129

关键词: SarcolemmaCystathionine gamma-lyasePinacidilMuscle relaxationKatp channelsChemistryAnatomyHuman airwayCytometryCell biologyGlibenclamide

摘要: Abstract Here we explored the impact of hydrogen sulfide (H2S) on biophysical properties primary human airway smooth muscle (ASM)–the end effector acute narrowing in asthma. Using magnetic twisting cytometry (MTC), measured dynamic changes stiffness isolated ASM, at single-cell level, response to varying doses GYY4137 (1–10 mM). slowly released appreciable levels H2S range 10–275 μM, and was long lived. In ASM cells, acutely decreased (i.e. an indicator relaxation) a dose-dependent fashion, decreases were sustained culture for 24 h. Human cells showed protein expressions cystathionine-γ-lyase (CSE; synthesizing enzyme) ATP-sensitive potassium (KATP) channels. The KATP channel opener pinacidil effectively relaxed cells. addition, pinacidil-induced relaxation completely inhibited by treatment with blocker glibenclamide. Glibenclamide also markedly attenuated GYY4137-mediated Taken together, our findings demonstrate that causes implicate as well role sarcolemmal Finally, given express intrinsic enzymatic machinery generating H2S, suggest thereby this class gasotransmitter can be further exploited potential therapy against obstructive lung disease.

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