Enhanced calcium release at specialised surface sites compensates for reduced t-tubule density in neonatal sheep...

Cardiac myocytes rely on transverse (t)-tubules to facilitate a rapid rise in calcium throughout the cell. However, despite their importance in triggering synchronous Ca²⁺ release, t-tubules are highly labile structures. They develop postnatally, increase in density during exercise training and are lost in diseases such as heart failure (HF). In the majority of settings, an absence of t-tubules decreases function. Here we show that despite reduced t-tubule density due to immature t-tubules, the newborn atrium is highly specialised to maintain Ca²⁺ release. To compensate for fewer t-tubules triggering a central rise in Ca²⁺, Ca²⁺ release at sites on the cell surface is enhanced in the newborn, exceeding that at all Ca²⁺ release sites in the adult. Using electron and super resolution microscopy to investigate myocyte ultrastructure, we found that newborn atrial cells had enlarged surface sarcoplasmic reticulum and larger, more closely spaced surface and central ryanodine receptor clusters. We suggest that these adaptations mediate enhanced Ca²⁺ release at the sarcolemma and aid propagation to compensate for reduced t-tubule density in the neonatal atrium.