Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane

Possibility of Venous Serum Cl− Concentration ([Cl−]s) as a Marker for Human Metabolic Status: Correlation of [Cl−]s to Age, Fasting Blood Sugar (FBS), and Glycated Hemoglobin (HbA1c)

The HCO3− concentration in venous serum ([HCO3−]s) is a factor commonly used for detecting the body pH and metabolic conditions. To exactly detect [HCO3−]s, the venous CO2 pressure should be kept as it is in the vein. The [HCO3−]s measurement is technically complicated to apply for huge numbers of almost heathy persons taking only basic medical examinations. The summation of [HCO3−]s and the venous serum Cl− concentration ([Cl−]s) is approximately constant; therefore, we studied if [Cl−]s could be a marker detecting metabolic conditions instead of [HCO3−]s. Venous blood was obtained from persons taking basic medical examinations (the number of persons = 107,630). Older persons showed higher values of [Cl−]s, fasting blood sugar (FBS), and glycated hemoglobin (HbA1c) than younger ones. [Cl−]s showed positive correlation to age and negative correlation to FBS and HBA1c. The negative correlation of [Cl−]s to FBS/HbA1c was obvious in persons with high FBS/HbA1c, leading us to an idea that persons with high FBS/HbA1c show high [HCO3−]s, which might be caused by low activity of carbonic anhydrase in the lung observed in persons with diabetes mellitus under acidotic conditions. Taken together, an easily measured serum electrolyte, [Cl−]s, could be a useful marker estimating metabolic conditions

Daidzein-Stimulated Increase in the Ciliary Beating Amplitude via an [Cl⁻]_i Decrease in Ciliated Human Nasal Epithelial Cells

The effects of the isoflavone daidzein on the ciliary beat distance (CBD, which is a parameter assessing the amplitude of ciliary beating) and the ciliary beat frequency (CBF) were examined in ciliated human nasal epithelial cells (cHNECs) in primary culture. Daidzein decreased [Cl−]i and enhanced CBD in cHNECs. The CBD increase that was stimulated by daidzein was mimicked by Cl−-free NO3− solution and bumetanide (an inhibitor of Na+/K+/2Cl− cotransport), both of which decreased [Cl−]i. Moreover, the CBD increase was inhibited by 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, a Cl− channel blocker), which increased [Cl−]i. CBF was also decreased by NPPB. The rate of [Cl−]i decrease evoked by Cl−-free NO3− solution was enhanced by daidzein. These results suggest that daidzein activates Cl− channels in cHNECs. Moreover, daidzein enhanced the microbead transport driven by beating cilia in the cell sheet of cHNECs, suggesting that an increase in CBD enhances ciliary transport. An [Cl−]i decrease enhanced CBD, but not CBF, in cHNECs at 37 °C, although it enhanced both at 25 °C. Intracellular Cl− affects both CBD and CBF in a temperature-dependent manner. In conclusion, daidzein, which activates Cl− channels to decrease [Cl−]i, stimulated CBD increase in cHNECs at 37 °C. CBD is a crucial factor that can increase ciliary transport in the airways under physiological conditions