title: Capacitation and Ca(2+) influx in spermatozoa: role of CNG channels and protein kinase G.
abstract: Cyclic guanosine monophosphate (cGMP) has been recently shown to modulate in vitro capacitation of mammalian spermatozoa, but the mechanisms through which it influences sperm functions have not been clarified. There are at least two targets of cGMP, cyclic nucleotide-gated (CNG) channels and cGMP-dependent protein kinase (PKG), involved in several physiological events in mammalian spermatozoa. It has been suggested that CNG channels allow the influx of Ca(2+) to cytoplasm during capacitation, whereas PKG could trigger a phosphorylation pathway which might also, indirectly, mediate calcium entry. Using the patch-clamp technique in whole-cell configuration, we showed how l-cis-Diltiazem (a CNG-channel inhibitor) and KT5823 (a PKG inhibitor) decreased significantly the amplitude of macroscopic ion currents in a dose-response manner, and decreased in vitro capacitation. The inhibition of CNG channels completely abolishes the Ca(2+) influx induced by cyclic nucleotides in mouse spermatozoa. This work suggests that the downstream cGMP pathway is required in mammalian sperm capacitation and the mechanisms involved include CNG channels and PKG, highlighting these molecules as important therapeutic targets for infertility treatments or to develop new male contraceptives.
authors.affiliation: Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México; Centro de Investigación y de Estudios Avanzados del IPN, Unidad Monterrey, Apodaca, Nuevo León, México.
authors.forename: A
authors.initials: A
authors.lastname: Cisneros-Mejorado
authors.forename: L
authors.initials: L
authors.lastname: Hernández-Soberanis
authors.forename: M C
authors.initials: MC
authors.lastname: Islas-Carbajal
authors.forename: D
authors.initials: D
authors.lastname: Sánchez
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors*; D004110:Diltiazem / Q000494:pharmacology; D017136:Ion Transport / Q000502:physiology; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013075:Sperm Capacitation / Q000187:drug effects / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D002227:Carbazoles; D054815:Cyclic Nucleotide-Gated Cation Channels; D047428:Protein Kinase Inhibitors; C073601:KT 5823; D017869:Cyclic GMP-Dependent Protein Kinases; D004110:Diltiazem; D006152:Cyclic GMP; D002118:Calcium
keywords: cGMP-dependent protein kinase; capacitation; cyclic guanosine monophosphate; cyclic nucleotide-gated channels; spermatozoa