Finally, HF upregulates IKs in HF SAN cells of rabbit (Verkerk et al., 2003), but since IKs plays a limited role in pacemaker activity without adrenergic stimulation (Lei et al., 2000), this change in membrane clock is hardly involved in the increase in intrinsic cycle length during HF (Verkerk et al., 2003). This evidence concerns the gene CLOCK and hydrops fetalis.