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. 2023 Jul 10;26(8):1365–1378. doi: 10.1038/s41593-023-01377-6

Fig. 3. Mouse model of heart failure is associated with leaky hippocampal RyR2.

Fig. 3

a, Cryogenic electron microscopy structure of RyR2 (gray, top and side view) showing the location of the Ser2808 in the RY3&4 phosphorylation domain (magenta) and calstabin2 (cyan). RyR2 PKA phosphorylation shifted the channel toward a primed state (yellow)50. b,c, Representative SDS–PAGE analysis and quantification of modified RyR2 and calstabin2 immunoprecipitated from hippocampal RyR2 complex (IP RyR2; bands normalized to total RyR2) in SHAM (n = 6), MI (n = 6), MI + ARM036 (n = 6), MI + S107 (n = 6), MI+ propranolol (n = 4) and MI + SD-208 (n = 4) mice. d, Single-channel traces of RyR2 incorporated in planar lipid bilayers with 150 nM Ca2+ in the cis chamber, corresponding to representative experiments performed with hippocampal samples from SHAM (n = 6), MI (n = 5), MI + ARM036 (n = 6), MI + S107 (n = 5), MI + propranolol (n = 5) and MI + SD-208 (n = 5) mice. e, RyR2 Po, To and Tc in the same groups. f, Ca2+ leak measured in microsomes from mouse hippocampi of the same groups. g, Bar graphs represent the quantification of Ca2+ leak as the percentage of uptake in SHAM (n = 6), MI (n = 6), MI + ARM036 (n = 6), MI + S107 (n = 6), MI + propranolol (n = 3) and MI + SD-208 (n = 3) mice. Individual values are shown with the mean ± s.e.m. One-way ANOVA and Tukey’s test post hoc correction for multiple comparisons shows *P < 0.05, SHAM versus MI or MI + ARM036; #P < 0.05, MI versus MI + S107, MI + propranolol or MI + SD-208. Data are derived from biologically independent samples. All statistical tests were two sided.

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