Activation of Ca2+ permeability by cAMP is coordinated through the pHi increase induced by speract

The egg peptide speract activates sperm K channels by transient stimulation of guanylyl cyclase (see the accompanying paper, Cook, S.P., and Babcock, D.F. (1993) J. Biol. Chem. 268, 22402-22407). Behavioral responses to speract are thought to require the brief elevations of cAMP and cytosolic [Ca2+] (Cai) also evoked by speract through yet unknown mechanisms. Here we present evidence that cAMP mediates activation of a putative, Mn(2+)-permeable Ca channel that is responsible for increased Cai. We find that: 1) prolonged elevation of Cai was produced by treatments previously shown to selectively enhance accumulation of cAMP; 2) elevation of Cai and entry of Mn2+ are prevented by those manipulations of external [Na+] and [K+] previously shown to prevent accumulation of cAMP; 3) the blockade to Ca2+ entry imposed by increased external K+ is bypassed by elevation of cytosolic pH (pHi) with NH4Cl; 4) in the absence of speract, NH4Cl allows Mn2+ entry that is enhanced by papaverine, an inhibitor of sperm cAMP phosphodiesterase. These results thus also suggest that elevation of pHi is both necessary and sufficient to activate adenylylcyclase. This study provides tentative identification of sperm Ca channels as downstream targets of cAMP action and indicates that pHi may determine whether cGMP- or cAMP-mediated second messenger pathways predominate in speract signal transduction.