Calsequestrin localization at RyR2 clusters enables calcium wave propagation in ventricular myocytes.

Co-localization of calsequestrin2 (CASQ2) with RyR2 clusters is required for robust calcium wave propagation in mouse ventricular myocytes, enabling reliable propagation at experimental-range velocities.

• Why it matters: Calcium waves must traverse 1-2 μm between Z-planes while being attenuated by cytosolic buffering and diffusion and while local RyR2 release depletes nearby sarcoplasmic reticulum calcium stores.
• What they did: A three-dimensional computational model of mouse ventricular myocytes at submicrometer resolution tested physiological CASQ2 concentration at release sites versus uniform CASQ2 distribution across the sarcoplasmic reticulum.
• The result: With CASQ2 concentrated at release sites, waves propagated reliably across the cell with velocities matching the experimental range, but with uniform CASQ2 distribution the wavefront stalled.