Extracellular Alkalinization Stimulates Calcium-activated Chloride Conductance in Cystic Fibrosis Human Airway Epithelial Cells

Cellular Physiology and Biochemistry

关键词: Extracellular pH;    Sodium;    Zinc;    Ca2+ entry;    Cl- channels;   

DOI  :  10.1159/000327967

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background The pH of the airway surface liquid (ASL) plays a pivotal role in maintaining the proper function of the respiratory epithelium. In patients with cystic fibrosis (CF) acidic ASL has been observed. Thus, alkalinization of ASL itself might be beneficial in CF. The aim of this study was to investigate the role of extracellular pH (pH_o) on the alternative Ca²⁺-activated Cl^- channels (CaCCs) in CF airway epithelial cells. Methods The [Ca²⁺]_i and viability of CF airway epithelial cells (IB3-1) were assessed using Fluo-3/AM and YO-PRO-1 fluorescent dyes, respectively. Ion currents were detected in whole-cell configuration using the patch clamp technique. Results Extracellular alkalinization (pH_o 8.2) stimulated Ca²⁺ entry and inward currents in low Na⁺ containing medium. The inward currents were blocked by the removal of extracellular Ca²⁺, chelating cytosolic Ca²⁺, as well as by the application of niflumic acid and DIDS. While Zn²⁺ promoted sustained Ca²⁺ entry in pH_o-dependent manner, it inhibited the anion conductance. The low external Na⁺ concentrations and alkaline pH_o were well tolerated by the cells. Conclusions Stimulation of CaCCs could be achieved by alkalinization of the extracellular environment in CF airway epithelial cells. Zn²⁺ directly blocked, however indirectly enhanced the activity of Cl^- conductance.

【 授权许可】

CC BY-NC-ND