Disordered yet functional atrial t-tubules on recovery from heart failure

Jessica L. Caldwell, Jessica D. Clarke, Charlotte E. R. Smith, Christian Pinali, Callum J. Quinn, Charles M. Pearman, Aiste Adomaviciene, Emma J. Radcliffe, Amy E. Watkins, Margaux A. Horn, Elizabeth F. Bode, Mark Eisner, David A. Eisner, Andrew W. Trafford, Katharine M. Dibb

Research output: Working paperPreprint

Abstract

Transverse (t)-tubules drive the rapid and synchronous Ca2+ rise in cardiac myocytes. The virtual complete loss of atrial t-tubules in heart failure (HF) decreases Ca2+ release. It is unknown if or how atrial t-tubules can be restored and if restored t-tubules are functional.

Sheep were tachypaced to induce HF and recovered when pacing was stopped. Serial block face Scanning Electron Microscopy and confocal imaging were used to understand t-tubule ultrastructure and function. Candidate proteins involved in atrial t-tubule recovery were identified by western blot and causality determined using expression studies.

Sheep atrial t-tubules reappeared following recovery from HF. Despite being disordered (branched, longer and longitudinally arranged) recovered t-tubules triggered Ca2+ release and were associated with restoration of systolic Ca2+. Telethonin and myotubularin abundance correlated with t-tubule density and altered the density and structure of BIN1-driven tubules in neonatal myocytes. Myotubularin had a greater effect, increasing tubule length and branching, replicating that seen in the recovery atria.

Recovery from HF restores atrial t-tubules and systolic Ca2+ and myotubularin facilitates this process. Atrial t-tubule restoration could present a new and viable therapeutic strategy.

Brief Summary: The loss of atrial transverse (t)-tubules and the associated dysfunction in heart failure is reversible and the protein myotubularin plays an important role.

Competing Interest Statement: The authors have declared no competing interest.
Original languageEnglish
PublisherbioRxiv
Pages1-3
Number of pages3
DOIs
Publication statusPublished - 28 Oct 2021

Publication series

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

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