Modular analysis of the control of flagellar Ca2+-spike trains produced by CatSper and CaV channels in sea urchin sperm
The structure is separated into 3 modules coupled by the membrane potential variable (V). In the Upstream module (described by the variables S, RF, RH, RL, G, , , and ) free receptors RF bind SAP molecules and transit irreversibly through three receptor forms, each with less guanylate cyclase activity: High RH, low RL and inactive RI; the cGMP synthesised by these receptors binds and opens KCNG channels, which conduct a hyperpolarising potassium current. The membrane hyperpolarisation promotes the opening of spHCN channels, which exert the opposite action on V when conducting a cationic inward current. Two candidate modules are presented to explain the calcium spike trains: one that includes classic voltage-dependent Ca2+ channels and BK channels (described by variables , , and ), and another that considers CatSper, NHE exchanger and proton concentration (described by , and H). Note in the CaV+BK module, that the calcium channel is purely voltage dependent, whereas CatSper in the other module has threefold regulation, namely Ca2+, H+ and V. The complexity of the CatSper channel is illustrated with two gates. Voltage-regulated channel transitions are depicted with blue arrows, where the darker or lighter tones indicate whether the transition is promoted by membrane hyperpolarisation or depolarisation respectively. The blue dotted lines linking some of these arrows to the membrane potential box top or bottom provide the same information. The components in the middle dashed boxes, namely cGMP (G), Ca2+ (C), proton (H) and membrane potential (V) are the main experimental observables. The ions K+ and Na+ are depicted in grey to indicate that the model describes only the currents while neglecting concentration changes.