Hyperabsorption of Na+ and raised Ca2+-mediated Cl- secretion in nasal epithelia of CF mice
Year: 2025
Type: article
Abstract: We investigated the effect of homozygous genetic disruption of the murine cystic fibrosis transmembrane regulator (CFTR) gene on regulation of the rates of Na+ absorption and Cl- secretion by nasal epithelia in cystic fibrosis (CF) mice. The basal in vivo nasal potential difference (PD; -28.8 ± 1.8 mV, n = 10) and amiloride-sensitive PD (Δ13.8 ± 1.0 mV, n = 10) were raised in CF mice compared with controls [-7.8 ± 0.8 mV, n = 14 (basal); Δ4.5 ± 0.7 mV, n = 14 (amiloride)], consistent with raised Na+ transport. In vitro studies of freshly excised nasal epithelia confirmed that CF epithelia exhibited a greater basal equivalent short-circuit current (I(eq);63.5 ± 12 μA/cm2, n = 15) vs. control (30.2 ± 7.2 μA/cm2, n = 16) and amiloride-sensitive I(eq) (Δ46.2 ± 12.5 μA/cm2) vs. control (Δ11.3 ± 4.5 μA/cm2). Tissue from normal mice failed to secrete Cl- in response to ionomycin (ΔI(eq): -1.2 ± 1.9 μA/cm2, n = 18), whereas CF murine tissue responded with a large rise in I(eq) (Δ55.1 ± 19.1 μA/cm2, n = 13). We conclude that CF murine nasal epithelia exhibit Na+ hyperabsorption, providing strong evidence for a regulatory link between CFTR and Na+ channel activity in airway epithelia. We speculate that upregulation of the Ca2+-mediated Cl- secretory pathway buffers the severity of airway disease in the CF mouse.
DOI: 10.17615/mswh-1f34
Authors: Boucher R.C., Vick R.N., Grubb B.R.
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4416236892
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