J Biol Chem 1993 Oct 25;26830:22402-7.

Selective modulation by cGMP of the K+ channel activated by speract.

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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.

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Genes referenced: LOC576642 LOC576733