Title: Cardiac T-Tubule Microanatomy and Function | Physiological Reviews
Headings: Cardiac T-Tubule Microanatomy and Function
Cardiac T-Tubule Microanatomy and Function
Abstract
I. INTRODUCTION
II. CARDIAC T-TUBULE STRUCTURE
A. History of T-Tubule Structure-Related Research
B. Gross Morphology and Geometry
C. Membrane Ultrastructure and Microdomains
1. cBIN1 microfolds: microdomains supporting LTCC-RyR dyads
2. Caveoli (caveolae): β-AR/LTCC signaling hubs
3. Ankyrin B microdomains: NCX/NKA/InsP 3 macromolecular complex
D. Peri-Membrane Cytoskeleton Scaffolds at Cardiac T-Tubules
1. Actin filaments, tropomyosin, and N-WASP
2. Costamere complex and t-tubule membrane-associated scaffolds
3. Myofilament structural proteins
E. Variation in Cardiac T-Tubule Geometry
III. TRANSMEMBRANE PROTEINS AT CARDIAC T-TUBULES
A. Ion Handling Proteins (Channels/Transporters/Pumps)
1. Ca 2+ handling proteins
2. Na + handling proteins
3. K + handling proteins
B. Signaling Molecules at Cardiac T-Tubules
IV. FUNCTION OF CARDIAC T-TUBULES
A. Dyad and EC Coupling
1. LTCC trafficking and clustering to dyads through BIN1
2. RyR recruitment to dyads through BIN1
3. Junctophilin-2 in t-tubule-jSR junctional membrane complex formation
B. Ion Diffusion and Membrane Excitability
C. Other Microdomain-Related Functions
V. LIFE CYCLE OF CARDIAC T-TUBULES
A. Membrane Biogenesis, Maintenance, and Turnover
B. Ion Channel Trafficking and Half-Life
VI. ALTERATION OF T-TUBULE STRUCTURE AND FUNCTION IN HEART FAILURE
VII. CONCLUSIONS
GRANTS
DISCLOSURES
Acknowledgments

Content: Cardiac t-tubules are also substantially remodeled during heart failure ( 38, 52, 89, 97, 98, 108, 130 - 134, 180, 202, 207, 208, 220, 224, 230 ). In addition to the observed loss and gross diminishment of the t-tubule network, protein components at t-tubules including ion channels and signaling molecules are reported to be either reduced at the t-tubule surface or redistributed elsewhere to non-t-tubule sarcolemma ( 20, 93, 134 ). Loss of complex t-tubules in heart failure not only causes impaired contractile function due to disrupted dyads and the resultant EC uncoupling, but also alters local concentration gradients and increases susceptibility to ventricular arrhythmia ( 66, 85, 91, 157, 163, 179, 181, 213 ). The molecular and cellular mechanisms of t-tubule remodeling in failing cardiomyocytes, in particular the alterations in t-tubule membrane ultrastructure and subdomains, is an active area of interest among cardiac biologists. This review summarizes and cites the current knowledge of cardiac t-tubule morphology, structure, components, and physiological functions, with emphasis on the organization and function of microdomains within t-tubules. The dynamic life cycle of t-tubule membrane and protein components, as well as the current understanding of microdomain remodeling in heart failure, will also be discussed. II. CARDIAC T-TUBULE STRUCTURE
A. History of T-Tubule Structure-Related Research
Striated muscle cells have a unique membrane system, the transverse-tubules (t-tubules), or more precisely, the transverse-axial-tubular system. T-tubules are sarcolemma invaginations formed by membrane tubules that are primarily perpendicular to myocyte longitudinal edges. These membrane tubular structures are interconnected in a complex network.