FIGURE 1.

Overview of K_V7 channel and PUFA molecular structures, and typified PUFA effects. (A) Schematic overview of K_V7 subtype expression and functional role. Note that these are examples, as some K_V7 subtypes have widespread expression and function. (B) Top view of K_V7.1 (PDB: 5VMS) with central pore domain in gray and peripheral voltage-sensing domains in black. Putative localization of KCNE at one K_V7.1 channel subunit is indicated [each subunit may accommodate one KCNE subunit (Sun and MacKinnon, 2020)]. Experimentally identified positively charged residues important for PUFA effects in K_V7.1 (Liin et al., 2018) are highlighted in red. Sequence alignment of the S6 site (important for G_max effect) and S4 site (important for V₅₀ effect) of all K_V7 isoforms are provided along with a side view of relevant channel domain. (C) Structure of the PUFA DHA, which has a carboxyl head linked to a 22-carbon long aliphatic tail with six cis double bonds. Deprotonation of the carboxyl head occurs at pH exceeding the pKa of the head-group, this endows DHA with a single negative charge. (D) Schematic overview of PUFA effect on current amplitude (I_Amp), mid-point of the G(V) curve (V₅₀), and maximum conductance (G_max) on indicated K_V7 subtypes. Please refer to Table 1 for further details. nd denotes not determined.