Lipopolysaccharide (LPS) hyperpolarizes the guinea‐pig tracheal epithelium (Epi) by increasing the activities of the epithelial sodium channel (ENaC) and the Na,K‐pump

Abstract

The administration of LPS (4 mg/kg, i.p.), which is involved in several airway inflammatory diseases, causes hyperpolarization of tracheal Epi at 18 h. This study set out to understand the mechanism(s) by which LPS causes hyperpolarization. In the isolated, perfused trachea preparation (IPT), LPS had no effect on epithelial ENaC or Na,K‐ATPase transcription or ENaC abundance, but doubled Na,K‐ATPase protein levels. In the presence of basolateral amphotericin B (AB, 7.5 μM) to short‐circuit the Na,K‐pump, apical amiloride (10 μM) inhibited transepithelial potential (Vt) to a greater extent in the LPS group compared to control. In the presence of apical AB to short‐circuit ENaC, the resulting Vt, due to the Na,K‐pump, was greater in the LPS group relative to control. In the Ussing chamber, readmission of K to the Epi Na‐loaded by K omission led to a greater hyperpolarization after LPS compared to control. Apical trypsin (100 U/ml) added to activate ENaC, increased Vt to a similar degree in control and LPS‐treated groups. Thus, LPS hyperpolarizes the Epi by increasing the activities of both ENaC and the Na,K‐pump. This may reflect alteration in their regulation. Funded by NIOSH