Apical volume expansion results in an immediate ENaC activation but in delayed onset of water resorption (718.1)

Abstract

Apical volume expansion results in an activation of the epithelial sodium channel ENaC. Its activation is proposed to facilitate water resorption and thus to counteract increases of apical surface liquid (ASL) volume e.g. in lung edema. In this study we investigated the adaptation of epithelial water resorption to apical volume expansion (AVE) in NCI‐H441 epithelia. Cells were cultivated at air‐liquid interface. AVE was introduced by adding isotonic NaCl solution onto the apical surface. Water resorption was measured by the recently established deuterium oxide dilution method (Neubauer et al. 2013, Anal Chem). ENaC channel activation was quantified in Ussing chamber experiments as amiloride sensitive short circuit currents. As expected, ENaC activity increases to its maximum within 15 min after AVE. Water resorption does not follow ENaC activation but starts 4 to 6 h after AVE. When ASL volume is reduced to 3.7 ±0.2 μl / 0.33 cm^2 water resorption stops and ENaC activity is reduced to basal levels. Our data demonstrate that AVE results in a rapid ENaC upregulation but ENaC activation is not the only trigger of onset of water resorption. However, off set of water resorption is associated with ENaC down regulation.Supported by BIU D.5007Grant Funding Source: Supported by BIU.5007