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

C.E.R. Smith, Jessica Clarke, Callum Quinn, Hana Najem, Zain Sultan, Nathan Denham, David Hutchings, George Madders, Jessica Caldwell, Lauren Toms, Christian Pinali, David Eisner, Andrew Trafford, Katharine Dibb

Research output: Working paperPreprint

Abstract

Transverse (t)-tubules ensure a uniform rise in calcium (Ca2+) 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 Ca2+ 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 Ca2+ 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 Ca2+ transient was maintained and this was associated with increases in the L-type Ca2+ current (ICa-L) and the Ca2+ content of the sarcoplasmic reticulum (SR). We suggest these changes are sufficient to overcome the elevated cytosolic Ca2+ buffering in the newborn and the decreased t-tubule density. We have shown the neonate atria is highly specialised to negate reduced central Ca2+ release through enhanced surface ICa-L and SR load. This maintains atrial function despite immature t-tubules highlighting important differences in Ca2+ handling in the newborn and heart failure atria where t-tubules are sparse.
Original languageEnglish
PublisherCold Spring Harbor Laboratory Press
DOIs
Publication statusPublished - 2 Oct 2023

Publication series

NamebioRxiv
PublisherCold Spring Harbor Laboratory Press
ISSN (Print)2692-8205

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