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Electrophysiological evidence for the presence of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse sperm
Author(s) -
FigueirasFierro Dulce,
Acevedo Juan José,
MartínezLópez Pablo,
Escoffier Jessica,
Sepúlveda Francisco V.,
Balderas Enrique,
Orta Gerardo,
Visconti Pablo E.,
Darszon Alberto
Publication year - 2013
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24166
Subject(s) - capacitation , cystic fibrosis transmembrane conductance regulator , sperm , microbiology and biotechnology , chloride channel , chemistry , cystic fibrosis , patch clamp , membrane potential , intracellular , protein kinase a , phosphorylation , tyrosine phosphorylation , biology , endocrinology , medicine , electrophysiology , biochemistry , neuroscience , genetics
Mammalian sperm must undergo a maturational process, named capacitation, in the female reproductive tract to fertilize the egg. Sperm capacitation is regulated by a cAMP/protein kinase A (PKA) pathway and involves increases in intracellular Ca 2+ , pH, Cl − , protein tyrosine phosphorylation, and in mouse and some other mammals a membrane potential hyperpolarization. The cystic fibrosis transmembrane conductance regulator (CFTR), a Cl − channel modulated by cAMP/PKA and ATP, was detected in mammalian sperm and proposed to modulate capacitation. Our whole‐cell patch‐clamp recordings from testicular mouse sperm now reveal a Cl − selective component to membrane current that is ATP‐dependent, stimulated by cAMP, cGMP, and genistein (a CFTR agonist, at low concentrations), and inhibited by DPC and CFTR inh ‐172, two well‐known CFTR antagonists. Furthermore, the Cl − current component activated by cAMP and inhibited by CFTR inh ‐172 is absent in recordings on testicular sperm from mice possessing the CFTR ΔF508 loss‐of‐function mutation, indicating that CFTR is responsible for this component. A Cl − selective like current component displaying CFTR characteristics was also found in wild type epididymal sperm bearing the cytoplasmatic droplet. Capacitated sperm treated with CFTR inh ‐172 undergo a shape change, suggesting that CFTR is involved in cell volume regulation. These findings indicate that functional CFTR channels are present in mouse sperm and their biophysical properties are consistent with their proposed participation in capacitation. J. Cell. Physiol. 228: 590–601, 2013. © 2012 Wiley Periodicals, Inc.