Camp- but not ca2+-regulated cl- conductance in epididymides and
seminal vesicles is defective in a cystic fibrosis mouse model.
Leung, A. Y. H., P. Y. D. Wong, J. R. Yankaskas, & R. C. Boucher.
Department of Physiology, The Chinese University of Hong Kong, Hong
Kong and Cystic Fibrosis Center, The University of North Carolina at
Chapel Hill, NC, USA
APStracts 3:0003C, 1996.
Cystic fibrosis (CF) reflects the loss of cAMP-regulated Cl- secretion
consequent to mutations in the cystic fibrosis transmembrane
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 and an alternative Ca2+-regulated
Cl- secretory pathways in primary cultures of the epididymides and
the seminal vesicles of normal and CF mice. The basal short-circuit
currents (Ieq) of cultures derived from the epididymides and the
seminal vesicles from the CF mice were lower (6.0+/-0.6, [mu]A.cm-2,
4.0+/-1.0 [mu]A.cm-2, respectively) than those from normal mice
(11.1+/-1.0 [mu]A.cm-2, 6.6+/-0.6 [mu]A.cm-2, respectively).
Forskolin induced significant Ieq responses in both the epididymis
(8.0+/-0.7 [mu]A.cm-2) and seminal vesicles (4.0+/-0.5 [mu]A.cm-2)
from normal mice, whereas forskolin-induced changes in Ieq in CF
mouse epididymis and seminal vesicles were absent, consistent with
defective cAMP-CFTR mediated Cl- secretion in CF mice. Ieq responses
to agonists (ionomycin, ATP) that raise intracellular Ca2+ (Ca2+i)
were larger than forskolin responses in normal animals (6.6+/-0.9
[mu]A.cm-2, 13.4+/-1.8 [mu]A.cm-2, respectively) and were preserved
in CF (6.5+/-0.9 [mu]A.cm-2, 17.1+/-1.0 [mu]A.cm-2, 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.
Received 8 May 1995; accepted in final form 20 December 1995.
APS Manuscript Number C261-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96