Subspace-located catalase prevents membrane degradation and dyssynchronization of local calcium release in adult cardiomyocytes

Catalase, a canonical antioxidant enzyme, has been shown to prevent maladaptive oxidative damage and protect against aging-associated deterioration of cellular functions. In cardiac tissue, catalase protects cardiac myocytes against a variety of pathological changes by maintaining normal contractile function. Here we elucidated how catalase can protect cardiomyocyte excitation-contraction (EC) coupling we focused on exploring the subcellular location and specific effects of catalase in cardiomyocytes. To determine the effects of catalase on cardiomyocyte EC-coupling, we used adenoviral overexpression and pharmacological inhibition of catalase with 3AT in cultured adult mouse ventricular myocytes combined with detailed characterization of Ca 2+ signaling. We found that endogenous catalase co-localizes with RyRs in the subspace between the junctional sarcoplasmic reticulum (SR) and t-tubules. When virally overexpressed, catalase increases the ROS scavenging capacity of myocytes and enhances Ca 2+ -release by increasing synchronization of local Ca 2+ -release. To improve Ca 2+ -release, catalase acts to prevent membrane peroxidation and prevents degradation of t-tubule structures. Both the functional and structural effects of catalase were reversed by catalase inhibition with 3AT. The effect of catalase on Ca 2+ -release was more pronounced in cardiomyocytes isolated from transverse aortic constriction-operated, hypertrophied mouse hearts. Overall, our data suggest that catalase located to the subspace has a specific role in stabilizing and protecting Ca 2+ -release structures from degradation in conditions associated with increased oxidative stress. • Endogenous catalase co-localizes with RyRs in mouse cardiomyocytes. • Virally overexpressed catalase increases Ca 2+ release of cardiomyocytes. • Catalase protects plasma membrane structures, including t-tubule from degradation. • Catalase increases synchronization of the local Ca 2+ -releases in cardiomyocytes.