Results described above, together with the observation here that cRNA ratios approximating those previously observed in human HF (Radicke et al., 2006) dramatically reduce total Kv4.3 current (Figure 9), strongly suggests that the relative balance of Kv4.3L and Kv4.3S is crucial to dictating Ito density and kinetics when co-assembled with β subunits known to regulate Kv4.3 in human heart, and raises the idea that therapeutic targeting to specifically upregulate Kv4.3S would be more beneficial in terms of Ito density restoration in HF than blanket Kv4.3 upregulation. Here, KCND3 is linked to hydrops fetalis.