cAMP- but not Ca2+-regulated Cl- conductance is lacking in cystic fibrosis mice epididymides and seminal vesicles
Year: 2025
Type: article
Abstract: Cystic fibrosis (CF) reflects the loss of adenosine 3',5'-cyclic monophosphate (cAMP)-regulated Cl- secretion consequent to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In humans, but not mice, with CF, the disease is associated with male infertility. The present study investigated the relative magnitudes of the cAMP pathways and an alternative Ca2+-regulated Cl- secretory pathway in primary cultures of the epididymides and the seminal vesicles of normal and CF mice. The basal equivalent short-circuit currents (I(eq)) of cultures derived from the epididymides and the seminal vesicles from the CF mice were lower (6.0 ± 0.6 and 4.0 ± 1.0 μA/cm2, respectively) than those from normal mice (11.1 ± 1.0 and 6.6 ± 0.6 μA/cm2, respectively). Forskolin induced significant I(eq) responses in both the epididymis (8.0 ± 0.7 μA/cm2) and seminal vesicles (4.0 ± 0.5 μA/cm2) from normal mice, whereas forskolin-induced changes in I(eq) in CF mouse epididymis and seminal vesicles were absent, consistent with defective cAMP-CFTR-mediated Cl- secretion in CF mice. I(eq) responses to agonists (ionomycin, ATP) that raise intracellular Ca2+ (Ca(i)/2+) were larger than forskolin responses in normal animals (6.6 ± 0.9 and 13.4 ± 1.8 μA/cm2, respectively) and were preserved in CF (6.5 ± 0.9 and 17.1 ± 1.0 μA/cm2, respectively). We speculate that the fertility of male CF mice is maintained by persistent expression of the predominant alternative Ca2+-mediated Cl- transport system in the epididymides and seminal vesicles.
DOI: 10.17615/xb7h-n726
Authors: Leung A.Y.H., Yankaskas J.R., Boucher R.C., Wong P.Y.D.
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: W4416224676
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