Single-channel recordings of hippocampal RyR2, reconstituted into planar lipid bilayers, revealed increased open probability (Po), increased mean open time (To) and decreased mean closed time (Tc) in individuals with HF compared to controls (Po = 0.19% ± 0.02%, To = 18 ± 2 ms, Tc = 58 ± 05 ms in HF hippocampi, n = 9; versus Po = 0.01% ± 0.002%, To = 2 ± 0.2 ms, Tc = 515 ± 52 ms in controls, n = 4; P < 0.05) in the presence of low, non-activating [Ca2+]cis (150 nM), conditions under which normal RyR2 channels are tightly closed (Fig. 1c,d). Here, RYR2 is linked to hydrops fetalis.