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A Chloride Channel in Rat Pancreatic Acinar AR42J Cells Is Sensitive to Extracellular Acidification and Dependent on ROS

A Chloride Channel in Rat Pancreatic Acinar AR42J Cells Is Sensitive to Extracellular Acidification and Dependent on ROS

Xiaoya Yang, Chan Zhao, Sana'a A Mahdy, Peisheng Xu, Meisheng Yu, Jiabao Wu, Liang Wang, Tim J Jacob, Linyan Zhu, Shuang Peng, Zhiqin Deng, Lixin Chen, Liwei Wang

Biochem Biophys Res Commun. 2020 Jun 4;526(3):592-598.

PMID: 32247607

Abstract:

Extracellular acidification, playing a promoting role in the process of acute pancreatitis, has been reported to activate Cl- channels in several types of cells. However, whether extracellular acidification aggravates acute pancreatitis via activating Cl- channels remains unclear. Here, we investigated the effects of extracellular acidification on Cl- channels in rat pancreatic acinar AR42J cells using whole-cell patch-clamp recordings. We found that extracellular acidification induced a moderately outward-rectified Cl- current, with a selectivity sequence of I- > Br- ≥ Cl- > gluconate-, while intracellular acidification failed to induce the currents. The acid-sensitive currents were inhibited by Cl- channel blockers, 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate and 5-Nitro-2-(3-phenylpropylamino) benzoic acid. After ClC-3 was silenced by ClC-3 shRNA, the acid-sensitive Cl- currents were attenuated significantly, indicating that ClC-3 plays a vital role in the induction of acid-sensitive Cl- currents. Extracellular acid elevated the intracellular level of reactive oxygen species (ROS) significantly, prior to inducing Cl- currents. When ROS production was scavenged, the acid-sensitive Cl- currents were abolished. Whereas, the level of acid-induced ROS was unaffected with silence of ClC-3. Our findings above demonstrate that extracellular acidification induces a Cl- current in pancreatic acinar cells via promoting ROS generation, implying an underlying mechanism that extracellular acidification might aggravate acute pancreatitis through Cl- channels.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP207233907	4,4′-Diisothiocyanatostilbene-2,2′-disulfonic acid disodium salt hydrate		207233-90-7	Price

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