Dopamine Regulates Amiloride‐Sensitive Epithelial Sodium Channel (ENaC) Activity in Alveolar Type 1 Cells Examined In Situ

Activation of ENaC is the initial, rate‐limiting step in ion/fluid transport. Alveolar type 1 (AT1) cells comprise >95% of the alveolar surface area and do express ENaC subunit protein, but whether AT1 cells have functional ENaC and contribute to lung fluid clearance is unclear. We used cell‐attached patch clamp methods to examine ENaC activity in AT1 cells from live 250μm sections of lung tissue. Fluorescent Erythrina crystagalli lectin was used to positively identify AT1 cells for patch experiments. In this way, we show for the first time single channel recordings of amiloride‐sensitive ENaC activity from AT1 cells in situ with conductances of 4.4pS (characteristic of highly selective cation channels, HSC) and 13.5 pS (non‐selective channels). 50nM amiloride blocked all HSC activity in AT1 cells. Immuno‐histochemical studies showed that AT1 cells express dopamine D1 and D2 receptors and that dopamine (DA) produced a dose‐dependent increase in ENaC activity in AT1 cells. Hence, DA may increase lung fluid clearance by increasing Na reabsorption in the alveolar epithelium.