Fig. 7. Proposed structural mechanisms of leaky RyR2 and its involvement in disease.

a, b Schematic representation of the normal function of RyR2 (a) and the pathological disease-related disfunction (b). In the case of disease variants, the resting state is in a subprimed/primed state, which correlates with the higher calstabin-2 k_off and Ca²⁺ leak during diastole under stress conditions. The orange object labeled “Cal” stands for calstabin. Figure 7a,b adapted from Marco C. Miotto et al., Structural analyzes of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment. Sci. Adv. 8,eabo1272(2022). 10.1126/sciadv.abo1272 under a CC BY license: https://creativecommons.org/licenses/by/4.0/.¹⁰ c Vicious cycle involved in heart failure progression and arrhythmias. Figure 7c was created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en.