1.A.6.3.2
FMRFamide (peptide)-gated  sodium channel, FaNaC.  The charge on aspartate-552 in TMS2 influcences the gating properties and potency of the channel (Kodani and Furukawa 2010; Kodani and Furukawa 2014).  The FMRFamide-evoked current through AkFaNaC was depressed 2-3-fold by millimolar (1.8 mM) Ca²⁺ (Fujimoto et al. 2017). Both D552 and D556 were indispensable for the sensitivity of FaNaC to millimolar Ca²⁺. The Ca²⁺-sensitive gating was recapitulated by an allosteric model in which Ca²⁺-bound channels are more difficult to open. The desensitization of FaNaC was also inhibited by Ca²⁺ (Fujimoto et al. 2017).  High-resolution cryo-EM structures of FaNaC in both apo and FMRFamide-bound states have been solved (Liu et al. 2023). AcFaNaC forms a chalice-shaped trimer and possesses several notable features, including two FaNaC-specific insertion regions, a distinct finger domain and non-domain-swapped TMS2 in the transmembrane domain (TMD). One FMRFamide binds to each subunit in a cleft located in the top-most region of the extracellular domain, with participation of residues from the neighboring subunit. Bound FMRFamide hass an extended conformation. FMRFamide binds tightly to A. californica FaNaC in an N terminus-in manner, which causes collapse of the binding cleft and induces large local conformational rearrangements. Such conformational changes are propagated downward toward the TMD via the palm domain, possibly resulting in outward movement of the TMD and dilation of the ion conduction pore (Liu et al. 2023).