Could the reorganization of ryanodine receptors account for the problems seen in failing hearts? To investigate, Kolstad et al. These receptors form clusters that allow them to synchronize when they open and close. It was not known what causes these changes, making it difficult to treat heart failure.Ĭalcium ions are released in cardiac muscle cells through protein channels called ryanodine receptors. In failing hearts, these increases in calcium ion levels are smaller, slower and less well coordinated. As a result the heart becomes inefficient, pumping less blood around the body.įor the cardiac muscle cells to contract, the levels of calcium ions in the cells needs to rapidly increase. During heart failure, these cells become less able to contract. The muscle cells of the heart coordinate how they contract and relax in order to produce the heartbeat. Thus, nanoscale RyR reorganization during HF augments Ca 2+ leak and slows Ca 2+ release kinetics, leading to weakened contraction in this disease. During the action potential, these slow sparks protracted and desynchronized the overall Ca 2+ transient. When successfully triggered, sparks in failing cells displayed slow kinetics as Ca 2+ spread across dispersed CRUs. Larger multi-cluster CRUs common in HF also exhibited low fidelity spark generation. An increased fraction of small CRUs in HF was linked to augmented ‘silent’ Ca 2+ leak, not visible as sparks. Functional groupings of RyR clusters which produce Ca 2+ sparks (Ca 2+ release units, CRUs) also became less solid. Using super-resolution imaging, we observed dispersion of RyR clusters in cardiomyocytes from post-infarction HF rats, resulting in more numerous, smaller clusters. We investigated whether this deficit can be traced to nanoscale RyR reorganization. Reduced cardiac contractility during heart failure (HF) is linked to impaired Ca 2+ release from Ryanodine Receptors (RyRs).

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