• PMID: 17588945
• Gene Name: CFTR
• Condition: Involved in the regulation of epithelial sodium channels(ENaC) during capacitation and thus contribute to the observed hyperpolarization associated with this process
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Involved in the regulation of epithelial sodium channels(ENaC) during capacitation and thus contribute to the observed hyperpolarization associated with this process

Involvement of cystic fibrosis transmembrane conductance regulator in mouse sperm capacitation

Hernández-González EO, Treviño CL, Castellano LE, de la Vega-Beltrán JL, Ocampo AY, Wertheimer E, Visconti PE, Darszon A.

Mammalian sperm acquire fertilizing ability in the female tract during a process known as capacitation. In mouse sperm, this process is associated with increases in protein tyrosine phosphorylation, membrane potential hyperpolarization, increase in intracellular pH and Ca2+, and hyperactivated motility. The molecular mechanisms involved in these changes are not fully known. Present evidence suggests that in mouse sperm the capacitation-associated membrane hyperpolarization is regulated by a cAMP/protein kinase A-dependent pathway involving activation of inwardly rectifying K+ channels and inhibition of epithelial sodium channels (ENaCs). The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl- channel that controls the activity of several transport proteins, including ENaCs. Here we explored whether CFTR is involved in the regulation of ENaC inhibition in sperm and therefore is essential for the capacitation-associated hyperpolarization. Using reverse transcription-PCR, Western blot, and immunocytochemistry, we document the presence of CFTR in mouse and human sperm. Interestingly, the addition of a CFTR inhibitor (diphenylamine-2-carboxylic acid; 250 microM) inhibited the capacitation-associated hyperpolarization, prevented ENaC closure, and decreased the zona pellucida-induced acrosome reaction without affecting the increase in tyrosine phosphorylation. Incubation of sperm in Cl- -free medium also eliminated the capacitation-associated hyperpolarization. On the other hand, a CFTR activator (genistein; 5-10 microM) promoted hyperpolarization in mouse sperm incubated under conditions that do not support capacitation. The addition of dibutyryl cyclic AMP to noncapacitated mouse sperm elevated intracellular Cl-. These results suggest that cAMP-dependent Cl- fluxes through CFTR are involved in the regulation of ENaC during capacitation and thus contribute to the observed hyperpolarization associated with this process. FAU - Hernández-González, Enrique O AU - Hernández-González EO AD - Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca Morelos 62210, México. eoton@cell.cinvestav.mx FAU - Treviño, Claudia L AU - Treviño CL FAU - Castellano, Laura E AU - Castellano LE FAU - de la Vega-Beltrán, José L AU - de la Vega-Beltrán JL FAU - Ocampo, Ana Y AU - Ocampo AY FAU - Wertheimer, Eva AU - Wertheimer E FAU - Visconti, Pablo E AU - Visconti PE