title: Electrophysiological evidence for the presence of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse sperm.
abstract: 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.
authors: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca Morelos, Mexico.
authors: Dulce
authors: D
authors: Figueiras-Fierro
authors: Juan José
authors: JJ
authors: Acevedo
authors: Pablo
authors: P
authors: Martínez-López
authors: Jessica
authors: J
authors: Escoffier
authors: Francisco V
authors: FV
authors: Sepúlveda
authors: Enrique
authors: E
authors: Balderas
authors: Gerardo
authors: G
authors: Orta
authors: Pablo E
authors: PE
authors: Visconti
authors: Alberto
authors: A
authors: Darszon
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D005260:Female; D019833:Genistein / Q000494:pharmacology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D013075:Sperm Capacitation / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism*; D053778:Thiazolidines / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
chemical_list: C482900:3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone; D001565:Benzoates; D050505:Mutant Proteins; D053778:Thiazolidines; D062367:ortho-Aminobenzoates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C001209:fenamic acid; D019833:Genistein