Bioelectric response of human nasal epithelial cells to polycationic protein

Polycationic proteins alter electrolyte transport by epithelium and endothelium, and in asthma are thought to disrupt the airway epithelium and contribute to hyperresponsiveness and airway plugging. In the present study, we used primary cultures of human nasal epithelial cells to investigate the response of respiratory tract epithelium to luminal presentation of a polycationic protein, protamine. Protamine (100 micrograms/ml) in the apical bathing solution had no significant effect on basal transepithelial resistance (Rt) but decreased short-circuit current (Isc) and hyperpolarized the apical membrane, indicating that Na+ absorption had been inhibited. Pretreating with amiloride inverted the response to protamine, resulting in an increase in Isc, depolarization of the apical membrane, and decrease in the fractional resistance of the apical membrane (fRa). The increase in Isc was inhibited by pretreatment with bumetanide. These results indicated that protamine augmented amiloride-induced Cl- secretion. Induction of Cl- secretion by bathing the apical surface in 3 mM Cl(-)-Ringer solution similarly resulted in protamine-induced depolarization of the apical membrane. Heparin precipitated protamine from solution and reversed the Isc responses. In summary, low concentrations of polycationic protein can alter electrolyte transport by human airway epithelium without desquamation, and the response is dependent on the secretory state of the tissue.