title: Selective modulation by cGMP of the K+ channel activated by speract.
abstract: The egg peptide speract stimulates sperm guanylyl cyclase and presumably enhances fertilization, but the roles of cGMP in sperm responses are yet undetermined. Here we show that speract-induced accumulation of cGMP or cAMP is selectively enhanced by the phosphodiesterase inhibitors, 3-isobutyl-1-methylxanthine (IBMX) or papaverine, respectively. These inhibitors provided the unusual opportunity to examine the consequences of manipulating cGMP- and cAMP-dependent responses. The following observations suggest that cGMP mediates activation of K channels, the earliest known ionic event in speract signal transduction: 1) both cGMP content and K+ permeability are maximal within 15 s of speract stimulation and both decline after intracellular pH (pHi) increases in response to hyperpolarization; 2) IBMX prolongs elevation of cGMP and sustains K+ permeability after pHi increases; 3) both cGMP accumulation and K+ permeability also are enhanced when the pHi increase is prevented by an elevated concentration of external K+ (Ko); 4) elevating pHi with NH4Cl bypasses the blockade imposed by high Ko and decreases K+ permeability. Because IBMX antagonizes this action of NH4Cl, these results further suggest that elevation of pHi initiates an inactivation of guanylyl cyclase that leads to K channel closure. However, K+ permeability is restored upon subsequent elevation of intracellular [Ca2+] (Cai), indicating either that sperm K channels possess an alternate regulatory mode, or that a distinct Ca(2+)-activated K permeability also participates in speract signal transduction. Regardless of the mechanism that mediates Cai action, sperm K channels are identified as downstream targets of cGMP and are implicated in a feedback loop that both terminates guanylyl cyclase activity and leads to their own inactivation.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle 98195.
authors.forename: S P
authors.initials: SP
authors.lastname: Cook
authors.forename: D F
authors.initials: DF
authors.lastname: Babcock
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000302:isolation & purification / Q000494:pharmacology*; D010208:Papaverine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012617:Sea Urchins; D012661:Semen / Q000737:chemistry; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D009842:Oligopeptides; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D000643:Ammonium Chloride; D019789:Tetraethylammonium; C028364:speract; D010208:Papaverine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP; D011188:Potassium; D015056:1-Methyl-3-isobutylxanthine; D004121:Dimethyl Sulfoxide