Measurement of Multi Ion Transport through Human Bronchial Epithelial Cell Line Provides an Insight into the Mechanism of Defective Water Transport in Cystic Fibrosis.

Miroslaw Zajac,Piotr Bednarczyk,Krzysztof Dolowy,Andrzej Lewenstam

doi:10.3390/membranes10030043

Abstract

We measured concentration changes of sodium, potassium, chloride ions, pH and the transepithelial potential difference by means of ion-selective electrodes, which were placed on both sides of a human bronchial epithelial 16HBE14σ cell line grown on a porous support in the presence of ion channel blockers. We found that, in the isosmotic transepithelial concentration gradient of either sodium or chloride ions, there is an electroneutral transport of the isosmotic solution of sodium chloride in both directions across the cell monolayer. The transepithelial potential difference is below 3 mV. Potassium and pH change plays a minor role in ion transport. Based on our measurements, we hypothesize that in a healthy bronchial epithelium, there is a dynamic balance between water absorption and secretion. Water absorption is caused by the action of two exchangers, Na/H and Cl/HCO3, secreting weakly dissociated carbonic acid in exchange for well dissociated NaCl and water. The water secretion phase is triggered by an apical low volume-dependent factor opening the Cystic Fibrosis Transmembrane Regulator CFTR channel and secreting anions that are accompanied by paracellular sodium and water transport.

Highlights

Epithelial tissue is made of a single layer of cells bound together by tight junctions
Final pH and transepithelial potential difference measured against the potential at basolateral medium
In the isosmotic transepithelial concentration gradient of either sodium or chloride ions, there is an electroneutral transport of the isosmotic solution of sodium chloride in both directions across the cell monolayer

Summary

Introduction

Epithelial tissue is made of a single layer of cells bound together by tight junctions. Water is transported across the epithelial cell layer by means of osmosis. Electroneutral transport of a single cation accompanied by a single anion causes the passive osmotic flow of 370 water molecules across the epithelium. In cystic fibrosis (CF), the anion transport route is impaired, which leads to defective ion and water transport across the epithelium and a too dense secreted mucus. Epithelial cells are polarized, i.e., there are different transporting molecules on both the apical and basolateral surfaces of the epithelial cells. There is a considerable number of different ion channels, transporters and pumps molecules that are present in epithelial cell membranes [1,2,3,4,5,6,7]

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