Transepithelial Ion Transport Properties of Human Native Small Airways

Abstract

Small airways are the crucial target in the pathogenesis of cystic fibrosis and other airway diseases. Characterization of transepithelial ion transport properties of small airways have been limited by their relative inaccessibility, mainly in native human tissue. We used our recently introduced micro‐Ussing chamber (area=1 mm2) to obtain the first measurements of ion transport properties of human native small airways specimens (<2 mm i.d.). Spontaneous open circuit transepithelial potentials (Vt), conductance (Gt) and equivalent short circuit current were measured. In presence of Cl− gradient Vt hyperpolarized and Gt decreased significantly. In symmetric NaCl, activating Cl− conductance with cAMP mediators (Fsk/IBMX) and purinergic agonist (UTP) evoked distinctly opposite effects on Vt, depolarizing and hyperpolarizing, respectively. Luminal amiloride depolarized Vt and decreased Gt significantly. Results suggest that human small airway epithelia express very high constitutively active Cl− conductance that support both secretory as well as absorptive functions. Small airways may consist of separate populations of secretory and absorptive cells that recycle airway surface fluids locally to maintain appropriate airway hydration and hygiene.Supported by the Nancy Olmsted Trust, NIH (R01‐HL084042) and American Lung Association California.