Ryanodine receptor dispersion disrupts Ca²⁺ release in failing cardiac myocytes.

ABSTRACT: Reduced cardiac contractility during heart failure (HF) is linked to impaired Ca²⁺ release from Ryanodine Receptors (RyRs). We investigated whether this deficit can be traced to nanoscale RyR reorganization. Using super-resolution imaging, we observed dispersion of RyR clusters in cardiomyocytes from post-infarction HF rats, resulting in more numerous, smaller clusters. Functional groupings of RyR clusters which produce Ca²⁺ sparks (Ca²⁺ release units, CRUs) also became less solid. An increased fraction of small CRUs in HF was linked to augmented 'silent' Ca²⁺ leak, not visible as sparks. Larger multi-cluster CRUs common in HF also exhibited low fidelity spark generation. When successfully triggered, sparks in failing cells displayed slow kinetic

SUBMITTER: Kolstad TR 

PROVIDER: S-EPMC6245731 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature