Chemotactic signaling pathway in sea urchin sperm. Resact, the chemoattractant peptide, binds to receptor GC and, thereby, stimulates the rapid synthesis of cGMP. The ensuing surge in cGMP opens K⁺-selective cyclic nucleotide–gated (CNGK) (Strünker et al., 2006; Galindo et al., 2007; Bönigk et al., 2009) channels to produce a brief hyperpolarization of the cell membrane. This hyperpolarization activates two other signaling components: an NHE and a hyperpolarization-activated cyclic nucleotide–gated (HCN) channel (Gauss et al., 1998; Galindo et al., 2005). NHE activity causes a rapid alkalinization of the cytosol (Lee, 1984; Lee and Garbers, 1986). Upon opening of HCN channels, the ensuing Na⁺ inward current depolarizes the cell and leads to the opening of voltage-dependent Ca²⁺ channels (Ca_v). Recovery from stimulation involves restoration of resting [Ca²⁺]_i by a Na⁺–Ca²⁺–K⁺ exchanger (NCKX) (Su and Vacquier, 2002) and hydrolysis of cGMP by a phosphodiesterase (PDE) (Su and Vacquier, 2006). The physiological role of a soluble adenylate cyclase (not depicted) (Nomura et al., 2005) and of the second messenger cAMP is not known.