SLC26A7 Can function as a chloride-loading mechanism in parietal cells

Abstract

To date three potential candidates for parietal cell basolateral Cl(-) entry have been described: the highly 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive Cl(-)/HCO(3)(-) exchanger AE2, the HCO(3)(-) and lowly DIDS-sensitive SLC26A7 protein, and the Na(+)-2Cl(-)K(+) cotransporter (NKCC1). In this study we investigate the contribution of these pathways to secretagogue stimulated acid secretion. Individually hand-dissected rat gastric glands were microfluorimetrically monitored for Cl(-) influx and pH(i) changes. Transporter activity was determined by varying ion content and through the use of pharmacological inhibitors. Expression of SLC26A7 in rat parietal cells was shown by immunohistochemistry and Western blot. SLC26A7 was inhibited by 5-Nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB) (100 microM) in the Xenopus laevis oocyte expression system. Cl(-) influx in parietal cells was enhanced by histamine, depended partially on endogenous HCO(3)(-) synthesis and completely on extracellular Na(+). Removal and subsequent readdition of Cl(-) revealed a low and a high DIDS-sensitive HCO(3)(-) extrusion system contributing to Cl(-) uptake. At acidic pH(i), however, H(+) extrusion via the H(+),K(+)-ATPase depending on Cl(-) uptake was abolished only in the presence of 100 microM (NPPB) and at high (250 microM) DIDS concentration. There was no effect of the NKCC inhibitor bumetanide on stimulated H(+) extrusion. These results would be compatible with SLC26A7 as a Cl(-) uptake system under histamine stimulation.

The Solute Carrier 26 Family of Proteins in Epithelial Ion Transport

“…An interesting feature of SLC26A7 is its regulation by pH i , with acidic pH i increasing the selectivity of SLC26A7 to Cl - (49). The physiological role of SLC26A7 is not known at present, but it may function as a Cl -loading mechanism in parietal cells (53). A pH i -regulated Cl -channel may serve as a sensor of pH i in cells that secrete acid or base equivalents to tighten their plasma membrane Cl -selectivity and favor coupled on the expense of uncoupled Cl -transport.…”

Ion Transporter NKCC1, Modulator of Neurogenesis in Murine Olfactory Neurons

“…The third highest expressed ion transporter in the OE was the DIDS-sensitive Cl Ϫ /HCO3 Ϫ -exchanger Slc26a7. This transporter is thought to accumulate chloride ions in different cell types (51,52). In contrast, when expressed in Xenopus laevis oocytes or HEK293 cells, human SLC26A7 functions as a pH iregulated Cl Ϫ -channel with minimal OH/HCO 3 -permeability (53).…”

Basics of gastric acid secretion

“…Для этого на базолатеральной мембране действует другая транспортная система, обеспечивающая обмен внутриклеточного аниона НСО 3 -на внеклеточный ион Сl -, которая называется НСО 3 -/Сl --анионообменником (SLC4A2) [2]. Помимо этого, источником ионов Сl -являют-ся базолатеральный котранспортер NKCCl и Сl --канал SLC26A7 [2,24,25]. Анионы НСО 3 -, в свою очередь, появ-ляются в клетке благодаря функционированию карбоан-гидразы, цитозольного фермента, обеспечивающего син-тез НСО 3 -из углекислого газа, постоянно образующе гося [6,19,20].…”