Atrial t-tubules adopt a specialist developmental state while alterations to Ca2+buffering maintain systolic Ca2+during postnatal development

Transverse (t)-tubules ensure a uniform rise in calcium (Ca 2+ ) and thus contraction in cardiac cells. Though more extensively studied in the ventricle, t-tubules also play a key role in the atria of large mammals, such as human, and their loss in heart failure is associated with impaired Ca 2+ release and thus contractility. T-tubule restoration is therefore an ideal therapeutic target but the process of t-tubule formation is not understood. The aim of this study was to determine how t-tubules develop in the healthy atria and the impact this has on Ca 2+ handling. Postnatal development was assessed in sheep from newborn through to adulthood. Atrial t-tubules were present at birth in the sheep atria and increased in density up until 3 months of age. In the latter part of development (3 months to adult) a lack of t-tubule growth but increase in cell width results in t-tubule density decreasing. In the newborn, despite reduced t-tubule density, we found the amplitude of the Ca 2+ transient was maintained and this was associated with increases in the L-type Ca 2+ current ( I Ca-L ) and the Ca 2+ content of the sarcoplasmic reticulum (SR). We suggest these changes are sufficient to overcome the elevated cytosolic Ca 2+ buffering in the newborn and the decreased t-tubule density. We have shown the neonate atria is highly specialised to negate reduced central Ca 2+ release through enhanced surface I Ca-L and SR load. This maintains atrial function despite immature t-tubules highlighting important differences in Ca 2+ handling in the newborn and heart failure atria where t-tubules are sparse.